bluuebunny/crossref_metadata_2025 huggingface dataset:
IMMUNOLOGICAL MEMORY IN MICE
Authors: Mitchell G. F. , Chan Eva L. , Noble Marion S. , Weissman I. L. , Mishell R. I. , Herzenberg L. A.
Published: June 2004

Using anti-allotype sera and AKR anti θC3H sera, a requirement for two cell types has been demonstrated in the adoptive secondary response of mice to heterologous erythrocytes. The cell types have been designated B cells [precursors of plaque-forming cells (PFC)] and T cells (thymus-influenced cells, not providing precursors of detectable PFC). The in vivo indirect PFC response of spleen cells from primed mice is markedly reduced by in vitro treatment of the cells with a mixture of anti-θ serum and guinea pig serum (Anti θ + GPS). This B cell response is fully restored to control levels by thymus cells from normal mice which do not themselves provide precursors of indirect PFC. Thus memory is carried by the B cell lineage but the expression of this memory is dependent on the presence of a cell population which is sensitive to Anti θ + GPS and which is replaced functionally by unprimed T cells. When assayed for T cell activity, thoracic duct cells from specifically primed mice are better than cells from nonspecifically primed mice in restoring the B cell response of spleen cells from immunized mice. Moreover, the T cell activity of a reconstitutive cell population from primed mice is reduced by incubation with Anti θ + GPS. We conclude that memory to heterologous erythrocyte antigens is carried by the T cell lineage as well as the B cell lineage even though unprimed T cells are sufficient for expression of B cell memory.
THE LIFE-SPAN AND RECIRCULATION OF MARROW-DERIVED SMALL LYMPHOCYTES FROM THE RAT THORACIC DUCT
Authors: Howard Jonathan C.
Published: June 2004

These experiments describe the preparation of pure marrow-derived lymphocyte suspensions from the thoracic duct of thymectomized, irradiated rats reconstituted with bone marrow cells. The majority of marrow-derived cells were small lymphocytes morphologically indistinguishable from small lymphocytes in thoracic duct lymph of normal donors.

Marrow-derived small lymphocytes (B lymphocytes) were a predominantly long-lived population; the frequency of short-lived B lymphocytes in the thoracic duct was not significantly higher than the frequency of short-lived small lymphocytes in normal lymph.

B lymphocytes transferred to normal recipients recirculated from blood to lymph. The first appearance of intravenously injected B lymphocytes in the thoracic duct was delayed relative to lymphocytes from normal donors and there was no clear cut modal recirculation time. Nevertheless their recirculation over a 48 hr period after transfusion was of the same order of magnitude as that of lymphocytes from normal donors.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Lee Chi-Jen , Dubos René
Published: June 2004

The metabolism of adenosine 3',5'-monophosphate (cyclic AMP) was studied in specific pathogen-free mice exposed to neonatal infection with mouse enterovirus or to malnutrition during early life. Metabolic activity was determined by measuring the turnover of cyclic AMP-8-14C to respiratory 14CO2, its incorporation into various organs and plasma, and the binding activity of synaptosome for cyclic AMP.

Early malnutrition increased the catabolism of cyclic AMP as measured by expiration in respiratory CO2. The level of cyclic AMP was lower in plasma and its incorporation into various tissues was decreased in infected and malnourished animals. Metabolic products of cyclic AMP were isolated from plasma by ion exchange chromatography. Cyclic AMP-8-14C had completely disappeared 9 hr after injection. Fewer metabolites of cyclic AMP were detected in infected or malnourished groups than in controls and the metabolic reaction from 5'-AMP to adenosine seemed to be slow in these animals. The ability to incorporate cyclic AMP to synaptosome was also impaired in the experimental groups.

The concentrations of brain cyclic AMP were lower in infected or malnourished animals than in controls. Depression of accumulation of cyclic AMP probably resulted from excessive activity of phosphodiesterase, rather than from impairment of adenyl cyclase. Intraperitoneal administration of theophylline brought the activity level of phosphodiesterase to normal in infected or malnourished mice; this fact probably accounted for enhanced accumulation of brain cyclic AMP.
THE PATHOGENESIS OF CHRONIC INFLAMMATION IN EXPERIMENTAL ANTIGEN-INDUCED ARTHRITIS
Authors: Cooke T. Derek , Hurd Eric R. , Ziff Morris , Jasin Hugo E.
Published: June 2004

In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera.

The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of 125I-labeled-inducing antigen to menisci from arthritic joints of immunized animals.

The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.
STUDIES ON THYMUS FUNCTION
Authors: Stutman Osias , Yunis Edmond J. , Good Robert A.
Published: June 2004

The immune functions of neonatally thymectomized C3Hf mice exposed only temporarily to thymus function show a progressive decay with time in the absence of the thymus. The immune responses studied at different ages in the range of 100–600 days were: first-set rejection of H-2-compatible and incompatible skin allografts, second-set rejection of skin allografts, capacity of spleen cells to produce graft-versus-host reactions in F1 hybrids, resistance to infection with mouse hepatitis virus, and response of spleen cells to phytohemagglutinin in vitro. These long-term studies had the purpose of determining the duration of the restoration induced by thymus function when the mice were exposed only temporarily to it. Different models were used but the two basic ones were: (a) mice grafted intraperitoneally at 15 days of age with a syngeneic thymus that was removed surgically at 10, 20, or 30 days after grafting, and (b) mice grafted at 15 days of age with allogeneic strain A thymoma or C57BL thymus, these representing situations in which there is spontaneous rejection of the restoring graft. In all the experimental models used, the animals were restored when tested at 100 days of age, but progressively became immunologically incapacitated at 200–300 days of age. From the more controlled experiments in which the restoring thymus graft was removed surgically, the following conclusions can be drawn. (a) A short exposure to a thymus graft can produce restoration of immune functions in neonatally thymectomized mice, but this restoration is not self-sustaining in the absence of the thymus and declines progressively with age. The decline usually starts at 200–300 days of age. (b) This was especially clear in experiments in which the same animal was tested twice in its lifetime for capacity to produce graft-versus-host reactions; these animals were competent at 100 days and became incompetent at 400 days of age. (c) The shortest period of thymic exposure studied was 10 days; if vascularization of the graft is taken into account, 2–3 days of thymic function are sufficient to produce restoration. (d) The immune decay observed in the thymectomized animals exposed temporarily to thymus was more profound than the physiological decay of immunity observed in control animals of similar age. (e) Of all the tests studied, the response of spleen cells to phytohemagglutinin was to be preserved the longest in animals exposed only temporarily to thymic function.

The present results were interpreted in accordance with our previous findings indicating that a population of postthymic cells can be developed by temporary exposure of neonatally thymectomized animals to thymic function, but that this population is not self-sustaining in the absence of thymus and progressively decays by physiological attrition.
THE RELATIONSHIP OF THE CHEMOTACTIC BEHAVIOR OF THE COMPLEMENT-DERIVED FACTORS, C3a, C5a, AND C567, AND A BACTERIAL CHEMOTACTIC FACTOR TO THEIR ABILITY TO ACTIVATE THE PROESTERASE 1 OF RABBIT POLYMORPHONUCLEAR LEUKOCYTES
Authors: Becker Elmer L.
Published: June 2004

The inhibition profiles obtained when a series of p-nitrophenyl ethyl alkylphosphonates and of p-nitrophenyl ethyl chloroalkylphosphonates were used to interfere with the chemotactic activity of polymorphonuclear leukocytes stimulated by C3a, C5a, and bacterial factor were the same as found previously when C567 was the chemotactic agent. This indicates that as in the chemotactic activity induced by C567, an obligatory step in the chemotaxis caused by C3a, C5a, and bacterial factor is the activation of proesterase 1 of the rabbit polymorphonuclear leukocyte.

C5a and C3a activate proesterase 1 of peripheral blood polymophonuclear leukocytes as measured by the increase of acetyl DL-phenylalanine ß-naphthyl esterase activity. Attempts to detect in a like manner the proesterase 1 of the same leukocytes using bacterial factor under varying circumstances have consistently failed. It is concluded that bacterial factor, for unknown reasons, is unable to activate proesterase 1 to the same extent as the complement-derived chemotactic factors.

The hypothesis of there being a quantitative difference in the ability of bacterial factor to activate proesterase 1 compared with the complement-derived factors explains the previous observations that bacterial factor can not deactivate to itself or to the complement-derived factors, although these latter factors can deactivate to themselves, to each other, and to the bacterial factor.

The quantitative difference in the ability of bacterial factor to activate proesterase 1 compared to the complement-derived factors is also associated with and explains the finding that the maximal chemotactic activity attainable when bacterial factor is the chemotactic agent is distinctly less than that obtained using either C3a, C5a, or C567.

These results indicate that the activation of proesterase 1 is a general requirement for the chemotactic activity of rabbit polymorphonuclear leukocytes with known macromolecular chemotactic agents and suggest that under several different circumstances the level of chemotactic activity attained is related to the degree of such activation.
CHRONIC ALLOGENEIC DISEASE
Authors: Gleichmann Helga , Gleichmann Ernst , André-Schwartz Janine , Schwartz Robert S.
Published: June 2004

The pathogenesis of glomerulonephritis in F1 hybrid mice injected with parental spleen cells was investigated in several ways. Whenever glomerulonephritis developed, the lesion had the typical morphology produced by antigen-antibody complexes. Experiments employing backcross mice demonstrated that the antigen is supplied by the recipient and that it is specified by the H-2 gene complex, or by a locus closely linked to H-2. The source of the antibody was investigated by staining glomerular lesions with fluorescein isothiocyanate-tagged anti-immunoglobulin allotype sera. Only donor-type allotypes could be detected. The ability of the donor's immunocytes to respond to the recipient's histocompatibility antigens in such a way as to produce nephritogenic immune complexes varied from strain to strain, and seemed to be controlled by a gene unrelated to H-2. The results suggest that cell surface antigens, such as histocompatibility antigens, may be of importance in the pathogenesis of several kinds of glomerulonephritis.
ELECTRON MICROSCOPE STUDY OF SURFACE IMMUNOGLOBULIN-BEARING HUMAN TONSIL CELLS
Authors: Zucker-Franklin Dorothea , Berney Steven
Published: June 2004

Surface immunoglobulin-bearing cells were selected from suspensions of human tonsil cells by the reverse immune cytoadherence technique. The method employed a hybrid antibody directed against Ig on lymphoid cells and against ferritin bound to sheep red blood cells (SRBC). Only 6% of the cells formed rosettes. When subjected to electron microscopy they were shown to consist of a morphologically heterogeneous population of cells. However, most cells in the center of rosettes showed ribosome-associated endoplasmic reticulum (RER) and polyribosomes. Usually these organelles were located in close proximity to membrane sites where a 400–600 A bridge was resolved between the lymphocyte and the ferritin particle on the SRBC. The bridge is postulated to consist at least in part of Ig. Only 50% of the plasma cells formed rosettes and bridges could not be resolved. The surface of the plasma cells within rosettes differed from that of plasma cells which had not reacted with ferritin-coated sheep erythrocytes. The incidence of plasma cells and γ-globulin-bearing lymphoid cells was corroborated with the help of fluorescent antibody techniques.
DISEASE ACCOMPANYING IN UTERO VIRAL INFECTION
Authors: Oldstone Michael B. A. , Dixon Frank J.
Published: June 2004

Early, after in utero infection with LCM virus, SWR/J and HA/ICR mice developed manifestations of immune complex disease. Observations based on nursing such mice with virus-infected, immune, or noninfected mouse mothers indicated that maternal antiviral antibody was responsible for the early immune complex glomerulonephritis. Despite comparable viral persistance, in utero-infected offspring failed to develop glomerulonephritis when nursed by noninfected mouse mothers, but did when suckled by virus-infected mouse mothers. Nursing by mouse mothers carrying high titers of anti-LCM viral antibody markedly enhanced the Ig glomerular deposits and the resultant nephritis.
THE UROPOD-BEARING LYMPHOCYTE OF THE GUINEA PIG
Authors: Rosenstreich David L. , Shevach Ethan , Green Ira , Rosenthal Alan S.
Published: June 2004

In this study, the frequency of uropod formation and the type of lymphocyte bearing the uropod was investigated in various guinea pig lymphocyte populations. Without prior in vitro stimulation, almost 40% of peritoneal exudate lymphocytes (PELS) form uropods, while thymocytes and lymph node cells form far fewer. Subsequent stimulation in vitro with purified protein derivative demonstrated that there is an association between antigen reactivity and frequency of uropod formation in these populations. The ultrastructure of these uropods is identical to that described for human lymphocytes stimulated with phytohemagglutinin. In the populations studied, all the lymphocytes forming uropods lack easily detectable surface membrane immunoglobulin and are therefore most likely thymus-derived or T lymphocytes.
SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE
Authors: Tigelaar Robert E. , Asofsky Richard
Published: June 2004

A mortality assay was used to quantitate graft-versus-host (GVH) reactions in sublethally irradiated (400 R) neonatal (C57BL/6 x BALB/c)F1 recipients of BALB/c lymphoid cells from various tissues. The probit of the 35 day cumulative per cent of mortality was a linear function of the logarithm of the cell inoculum for any tissue; reactivities of different tissues fell on a series of parallel lines. Peripheral blood leukocytes (PBL), the most active cells, were about 30 times as active as thymocytes, the least active cells studied; femoral lymph node cells and spleen cells were about 23 and 8 times as reactive as thymocytes, respectively. The average survival time of recipients of thymocytes who eventually died was nearly a week longer than that of recipients of comparably lethal numbers of PBL, lymph node, or spleen cells.

Mixtures of PBL and thymocytes gave levels of 35 day mortality significantly greater than those expected if the reactivities of the mixture had been merely the sum of the reactivities of the components measured separately, thereby confirming in any assay independent of host splenomegaly the synergistic interaction of thymocytes and PBL in the GVH reaction. Both populations of cells in the mixture had to be allogeneic to the host in order to observe this synergy.

The kinetics of cumulative mortality observed for mixtures of PBL and thymocytes were indistinguishable from those seen with thymocytes alone, indicating activation of the latter cell type. Finally, comparison of the relative abilities of different cell populations to cause splenomegaly on the one hand and lethal runting on the other has raised the possibility that expression of different effector functions of cell-mediated immune reactions may in fact be initiated by distinct cells.
REQUIREMENT OF THYMUS (T) LYMPHOCYTES FOR RESISTANCE TO LISTERIOSIS
Authors: Lane F. C. , Unanue E. R.
Published: June 2004

Spleen cells of mice infected with Listeria monocytogenes were adoptively transferred to normal mice. Such lymphocytes conferred resistance to a lethal challenge with Listeria. Hyperimmunization of the donor reduces the number of cells necessary to transfer effective immunity. Such spleen cells if treated with anti-θ serum do not transfer resistance to Listeria. Hence, thymus (T) lymphocytes are involved in the resistance to infection with the facultative intracellular bacteria L. monocytogenes.
STUDIES ON THE MECHANISM OF FEVER ACCOMPANYING DELAYED HYPERSENSITIVITY
Authors: Atkins Elisha , Feldman Joseph D. , Francis Lorraine , Hursh Ellen
Published: June 2004

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization.

The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.
DEVELOPMENT OF CHICKEN LYMPHOID SYSTEM
Authors: Choi Yong Sung , Good Robert A.
Published: June 2004

Synthesis and secretion of Ig by chicken lymphoid cells was studied. Both spleen and bursa cells synthesize and secrete IgM and IgG whereas Ig was not detected in thymus cells. In contrast to the spleen cells which synthesize H and L chains in balanced quantities, the bursa cells synthesize and secrete free L chains. In addition to the lymphoid cells which secrete IgM or IgG, the bursa appears to contain a cell population which synthesizes nonsecretory Ig. The structure of this Ig was studied by specific serological precipitation and by SDS-acrylamide gel electrophoresis. The H chains of this nonsecretory Ig are serologically related to µ-chains and exhibit a smaller molecular weight (i.e., ∼50,000) in SDS-acrylamide gel electrophoresis than H chains of IgG and IgM synthesized by the spleen cells (i.e., ∼70,000).
FURTHER EVIDENCE CONCERNING THE AUTOANTIGENIC STATUS OF THE TROPHOBLAST
Authors: Beer Alan E. , Billingham R. E. , Yang S. L.
Published: June 2004

Heterologous antisera were raised by inoculation of rabbits with fairly pure suspensions of trophoblast, lymphoid, fetal (excluding placental components), epidermal, decidual, and renal cells from Fischer rats. After absorption of hemagglutinins, these antisera were assayed for abortifacient activity by intramuscular inoculation into time-mated Fischer females.

The anti-trophoblast serum aborted all the recipients, but had some nonspecific activity in that it caused the deaths of 12% of them. Anti-lymphocyte serum was more toxic and less potent as an abortifacient. None of the other sera harmed either the mothers or their fetuses. However, the anti-kidney cell serum caused kidney lesions.

Absorption of the anti-trophoblast serum with lymphoid cells completely removed its toxicity for the pregnant females without perceptible impairment of its abortifacient activity. However, the latter could be removed by absorption with trophoblast cells.

(a) The lymphocyte-absorbed anti-trophoblast serum was equally effective in aborting rats over the range 7–18 days postconception; (b) a single injection of 1 ml was sufficient in most cases, and (c) it was equally efficacious in terminating gestation in rats irrespective of their genetic constitution, and (d) its effect was highly species-specific.

These findings support the premise that a unique antigen (or antigens), of possible clinical significance, is associated with trophoblast cells.
IMMUNE STATUS OF MICE TOLERANT OF LIVING CELLS
Authors: Voisin G. A. , Kinsky R. G. , Duc H. T.
Published: June 2004

CBA mice were rendered highly tolerant to A/Jax cells by neonatal intravenous injections of (CBA x A)F1 spleen cells. The high degree of tolerance was ascertained by the absence of circulating antibodies detected in the sera by the usual tests and by the perfect state of A skin grafts during all the experiments. Tolerant sera (sera from tolerant animals) were studied at three periods of tolerance: before skin test grafting, from 2 to 11 wk after grafting, and at time of sacrifice at almost 6 months of age.

The tolerant sera were shown to have specific facilitation-enhancing properties promoting the take and growth of A/Jax sarcoma (SaI and /Sa 15091a grafted on normal CBA mice. These properties were present throughout the duration of the experiments, showing that they were not the result of a beginning interruption of tolerance. The tolerant sera, although lacking the usual serological properties (hemagglutination, hemolysis, cytotoxicity, passive cutaneous anaphylaxis) had, however, specific synergistic hemagglutinating properties (increasing the hemagglutinating titer of a reference immune serum). Antibodies giving direct specific hemagglutination could be extracted from spleens of 20% of highly tolerant mice. The tolerant sera were also found to contain more IgG1 and more IgA than normal sera while they contained normal quantities of the complement-fixing immunoglobulins IgG2 and IgM.

Fractionation of tolerant sera on DEAE chromatography column confirmed the data concerning immunoglobulin classes and demonstrated direct specific serological activities undetected in unfractionated sera: a weak hemolysis in the most cationic fractions and a weak hemagglutination in the middle fractions. Synergistic hemagglutination, detected in unfractionated serum, was localized in fast anionic fractions containing high IgA concentration, along with facilitation-enhancing activity, thus confirming a link suggested previously between these three properties.

The relation between immunological tolerance and facilitating antibodies was discussed in the light of the fact that antibodies, possibly of a particular class continuously present at low dose in the sera of highly tolerant animals, are able to transfer (at least partly) this state of tolerance provided a sensitive test system is utilized.
ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE
Authors: Alkan Sefik S. , Williams E. Brady , Nitecki Danute E. , Goodman Joel W.
Published: June 2004

L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT.

Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both.

Immunization with symmetrical bifunctional RAT-(SAC)n-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.
GENETIC CONTROL OF THE IMMUNE RESPONSE
Authors: McDevitt Hugh O. , Deak Beverly D. , Shreffler Donald C. , Klein Jan , Stimpfling Jack H. , Snell George D.
Published: June 2004

Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome. Both of these recombinants were derived from crossovers between the H-2K locus and the Ss-Slp locus near the center of the H-2 region. One of these recombinants, H-2y, was derived from a known single crossover event. These results indicate that Ir-1 lies near the center of the H-2 region between the H-2K locus and the Ss-Slp locus.

The results of a four-point linkage test were consistent with these results. In 484 offspring of a cross designed to detect recombinants between H-2 and Ir-1, only two putative recombinants were detected. Both of these recombinants were confirmed by progeny testing. Extensive analysis of one of them has shown that the crossover event occurred within the H-2 region. (Testing of the second recombinant is currently under way.) Thus, in the linkage test, recombinants between H-2 and Ir-1 are in fact intra-H-2 crossovers. These results permit assignment of Ir-1 to a position between the H-2K locus and the Ss-Slp locus.
IMMUNOSUPPRESSION OF MICE INJECTED WITH HETEROLOGOUS ANTI-IMMUNOGLOBULIN HEAVY CHAIN ANTISERA
Authors: Manning Dean D. , Jutila John W.
Published: June 2004

Neonatal injection of mice with rabbit anti-µ antiserum has been shown to produce complete loss of direct and indirect plaque-forming responses to sheep erythrocytes as well as loss of serum IgM and severe depressions of all other serum immunoglobulins. Similar injection of anti-γ1γ2 or anti-γ1 antibodies effects a loss of the indirect response but induces relatively minor alterations in serum Ig levels. Delaying initiation of anti-µ treatment until young adulthood results in a somewhat diminished effect on plaque-forming responses and serum Ig levels but triggers the release of high serum levels of an aberrant µ-bearing protein.

Anti-µ suppression of genetically thymusless mice indicates that at least part of the target cells for suppression are bone marrow derived. A working hypothesis for the maturation of humoral antibody-producing cell lines as it relates to these data is discussed.
CLASSIFICATION OF THYMUS-DERIVED AND MARROW-DERIVED LYMPHOCYTES BY DEMONSTRATION OF THEIR ANTIGEN-BINDING CHARACTERISTICS
Authors: Haskill J. S. , Elliott B. E. , Kerbel R. , Axelrad M. A. , Eidinger D.
Published: June 2004

Antigen-binding cells of T and B origin can readily be determined by quantitating the number of sheep erythrocytes per rosette after glutaraldehyde fixation. The T1 and T2 populations have low antigen-binding properties and are very unstable without fixation. The B1 and B2 populations are stable and correlate with precursor and secretory cells. Fixation of rosettes permits a sensitive test for studying differentiation of T and B cells.
POTENTIATION OF THE T-LYMPHOCYTE RESPONSE TO MITOGENS
Authors: Gery Igal , Waksman Byron H.
Published: June 2004

Effective supernatants (SUP), which potentiate mouse T-cell responses to phytohemagglutin (PHA), are obtained from cells of several species (human, rabbit, rat, mouse) and indeed from syngeneic spleen, thymus, or bone marrow cells. Unstimulated cells release some SUP activity but more is produced after stimulation. Lipopolysaccharide (LPS) produced very active SUP in all cultures tested. PHA was similarly active on human leukocytes only, whereas concanavalin A (Con A) gave highly efficient SUP only with mouse spleen cells. SUP production is not correlated with a mitotic response of the donor cells and is observed in cultures unable to respond mitotically to the stimulant. Adherent mouse spleen cell populations, consisting largely or entirely of macrophages, produce active SUP, while nonadherent cells do not. Similarly, purification of human peripheral leukocytes on nylon columns, with removal of macrophages and other adherent cells, destroys their ability to produce SUP. The importance of indirect effects in stimulating mitotic responses of T cells is emphasized by the fact that the mitotic response of mouse thymocytes to LPS and its ability to potentiate the response of these cells to PHA disappears with removal of adherent cells from the thymocyte population. Conversely the production of SUP from spleen cells stimulated by Con A requires the presence of T cells.
EXPERIMENTAL ALLERGIC ENCEPHALITIS
Authors: Spitler Lynn E. , von Muller Christine M. , Fudenberg H. Hugh , Eylar Edwin H.
Published: June 2004

The encephalitogenic determinant of brain protein, a nonapeptide having the amino acid sequence Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys, has been characterized and synthesized. In a previous study, analogues of this encephalitogenic peptide were synthesized and some were shown to be encephalitogenic while others were not. Guinea pigs were immunized with encephalitogenic peptides having amino acid sequences different from that in the native protein. These guinea pigs did not show cellular immunity in vivo (skin reactivity) or in vitro (lymphocyte stimulation or macrophage migration inhibition) to the encephalitogenic brain protein (EP) although they did show cellular immunity to the immunizing antigenic peptide. Guinea pigs immunized with an encephalitogenic peptide having the same amino acid sequence as the brain protein, or with a nonencephalitogenic peptide having the same amino acid sequence as the native protein but lacking the terminal lysine, did develop cellular immunity to the EP. Animals immunized with EP showed cellular immunity to this protein, but not to the encephalitogenic peptides. Animals immunized with nonencephalitogenic protein (NEP), prepared by altering the tryptophan residue of EP, did not develop disease but did show cellular immunity in vitro and in vivo to the EP. Animals protected from disease by immunization with NEP similarly showed cellular immunity to EP. Thus, the results suggest a dissociation between cellular immunity to EP and the production of experimental allergic encephalitis (EAE). Animals immunized with the encephalitogenic peptides develop EAE, but do not show cellular immunity to EP, and animals immunized with NEP show cellular immunity to EP but do not develop EAE. A fresh approach to the examination of the pathogenesis of EAE is now possible through the use of these well-characterized antigens.
THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES
Authors: Volkman Alvin
Published: June 2004

Radioautographs of infiltrative cells in the kidneys of (Lewis x BN)F1 rats labeled with tritiated thymidine (TdR3H) before the subcapsular injection of parental (Lewis) thoracic duct lymphocytes (TDL) showed a predominantly host-proliferative response by 4 days after grafting. The immediate renal incorporation of TdR3H was used to measure the local graft-vs.-host (GVH) reactions. Substantial reactions could still be induced in the face of the considerable degree of leukopenia after 400 R whole body γ-irradiation. These results suggest that radioresistant cells are capable of carrying on the appropriate host activities and that the weakness of GVH reactions induced after higher doses of irradiation may be due to impairment of the mitotic mechanism of host cells. The importance of circulating leukocytes as a source of immunogenic stimulation was nevertheless substantiated by inducing local GVH reactions with Lew TDL in chimeric parental-type rats that had been repopulated with F1 bone marrow. This result also emphasizes the nonspecific nature of tissue destruction in the renal GVH reaction in confirmation of Elkins. In this and other situations in which B cells were the predominant F1 type elements available for interaction with parental-type TDL the reactions were nearly equivalent or equivalent to those in the appropriate controls.

Typical local GVH reactions could be induced in heavily irradiated hosts by an inoculum of combined parental and F1-type TDL in the apparent absence of mononuclear phagocytes.

The possible relationship between the activation of host lymphocytes, the involvement of B cells, and the nonspecific nature of tissue damage in the renal GVH is discussed.
COMPLEMENT-DEPENDENT PLATELET INJURY BY STAPHYLOCOCCAL PROTEIN A
Authors: Hawiger Jacek , Marney Samuel R. , Colley Daniel G. , Des Prez Roger M.
Published: June 2004

A new example of complement-mediated platelet injury has been described. Staphylococcal protein A (SPA) causes rabbit platelet injury as manifested by release of platelet 5-hydroxytryptamine (5HT). This reaction is complement-dependent and occurs over a very small range of SPA concentration, larger amounts being inhibitory. Complement fixation by SPA demonstrates the same narrow SPA concentration requirement whereas precipitation of IgG by SPA is roughly proportional to SPA concentration over a wide concentration range. The reaction can be separated into a sensitization step which requires SPA and plasma but not complement, and a release step which does require complement.

Complement-mediated platelet damage induced by SPA is a new biologic property of this common component of the cell wall of pathogenic staphylococci which may contribute to the development of inflammatory and thromboembolic reactions complicating intravascular staphylococcal infection.
INFLUENCE OF DIETARY POTASSIUM AND SODIUM/POTASSIUM MOLAR RATIOS ON THE DEVELOPMENT OF SALT HYPERTENSION
Authors: Dahl Lewis K. , Leitl George , Heine Martha
Published: June 2004

Among genetically hypertension-prone rats, dietary sodium (chloride) was demonstrably hypertensinogenic and potassium (chloride) antihypertensinogenic.

On diets containing the same NaCl but different KCl concentrations, mean blood pressure was greater in rats receiving less dietary potassium, i.e., diets with a higher Na/K molar ratio.

On diets with different absolute concentrations of NaCl and KCl, but the same Na/K molar ratios, rats on the higher absolute NaCl intakes had the higher blood pressures.

On diets with different absolute concentrations of NaCl and KCl, and different Na/K molar ratios, a group on a lower absolute NaCl intake but with a higher Na/K ratio could have more hypertension than a group on a higher absolute NaCl intake but with a lower Na/K ratio.

At equivalent molar ratios, the respective effects of these two ions on blood pressure were dominated by that of sodium. It was concluded that the dietary Na/K molar ratio can be an important determinant for the severity, or even development, of salt-induced hypertension.

The mechanism of the moderating effect of potassium on sodium-induced hypertension was unclear.
BRAIN-ASSOCIATED STEM CELL ANTIGEN: AN ANTIGEN SHARED BY BRAIN AND HEMOPOIETIC STEM CELLS
Authors: Golub Edward S.
Published: June 2004

There is an antigen on mouse brain tissue which is shared by the hemopoietic colony-forming unit or stem cell of the mouse. Treatment of bone marrow or fetal liver cells with anti-brain antisera inhibits expression of colony-forming units. The anti-stem cell antibody is not absorbed by thymus cells and thus can be distinguished from the anti-thymocyte antibody which these antisera also contain.
ANTIBODY-MEDIATED SUPPRESSION OF GRAFTED LYMPHOMA CELLS
Authors: Shin Hyun S. , Kaliss Nathan , Borenstein David , Gately Maurice K.
Published: June 2004

Specific alloantibody admixed with a grafted murine lymphoma is suppressive of the graft in mice of the inbred strain native to the tumor. Suppressive capacity of the host is obviated in mice given 500 R whole body irradiation before tumor inoculation but is restored when normal peritoneal macrophages are admixed with the tumor-antibody inoculum. Other normal cell types admixed with the tumor-antibody inoculum are not effective in restoring suppressive capacity.
CLASS, SUBCLASS, AND ALLELIC EXCLUSION OF MEMBRANE-BOUND Ig OF HUMAN B LYMPHOCYTES
Authors: Fröland S. S. , Natvig J. B.
Published: June 2004

Membrane-bound immunoglobulins of peripheral blood B lymphocytes and of lymphocytes from an IgG chronic lymphocytic leukemia showed restriction to one immunoglobulin class, one IgG subclass, and one Gm allotype. Certain antigens in the C-terminal part of IgG Fc were not exposed on the cell surface.
THE ALLOGENEIC EFFECT IN INBRED MICE
Authors: Katz David H. , Osborne David P.
Published: June 2004

Experimental conditions have been established for the elicitation of an allogeneic effect on the adoptive transfer secondary anti-2,4-dinitrophenyl (DNP) antibody response in mice. Thus, spleen cells from DNP-keyhole limpet hemocyanin (KLH)-primed mice manifest good secondary anti-DNP responses to a challenge with DNP-KLH, but not with DNP-bovine gamma globulin (BGG), after adoptive transfer to irradiated syngeneic recipients. However, a good adoptive transfer secondary anti-DNP response of such cells can be elicited with DNP-BGG when a second transfer of allogeneic lymphoid cells, in appropriate numbers, is carried out 24 hr before secondary challenge. The advantage to this system is that the DNP-primed cell population as well as the population of allogeneic lymphoid cells are accessible to experimental manipulation such that the T lymphocytes of one or the other can be removed.

Utilizing this model, we have established that the allogeneic effect on antibody production can operate on a population of primed B lymphocytes which have been depleted of their isologous T lymphocytes by in vitro incubation with anti-θ serum plus complement. The potential cellular interactions involved in the mechanism of this phenomenon are considered and discussed in detail.
IMMUNITY AND TOLERANCE TO A HAPTEN (NIP) COUPLED TO AN ISOLOGOUS CARRIER (MOUSE GAMMA GLOBULIN)
Authors: Walters Curla S. , Moorhead John W. , Claman Henry N.
Published: June 2004

A hapten, 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) when coupled to isologous mouse gamma globulin (MγG) elicits a hapten-specific immune response in mice if administered in Freund's complete adjuvant. This response is measurable by the capacity of the sera to bind N125IP, by detection of NIP-specific plaque-forming cells (B cells), and by in vitro secondary type antigen-driven DNA synthesis (T cells and probably B cells). The in vitro response requires both the hapten and carrier since neither by itself is capable of stimulating the spleen cells. This same antigen gives rise to hapten-specific tolerance when given in the soluble form. Mice pretreated with soluble NIP-MγG and challenged with NIP coupled to a heterologous carrier give a normal antibody response to the carrier but have barely detectable levels of antibody to NIP. Spleen cells from mice made tolerant to NIP-MγG do not respond in vitro with increased DNA synthesis. This implies that thymus-derived cells as well as bone marrow-derived cells are involved in hapten-specific tolerance.
THE MIGRATION OF LYMPHOCYTES ACROSS THE VASCULAR ENDOTHELIUM IN LYMPHOID TISSUE
Authors: Schoefl G. I. ,   With an Appendix by R. E. Miles
Published: June 2004

An electron microscope study was made of the mode of lymphocyte migration across the endothelial layer of venules in the Peyer's patches of mice and rats. Single and serial sections were examined.

Of a total of about 800 lymphocytes observed in single sections, 91% were located between endothelial cells and 9% were surrounded by endothelial cytoplasm in the particular plane of section. 62% of the lymphocytes occurred in groups of two or more. In long sequences of serial sections through 21 endothelial cells, all lymphocytes were located external to the endothelial cells though some appeared "internal" at certain levels of sectioning.

The probability that a lymphocyte which appears to be surrounded by endothelial cell cytoplasm actually lies within the cell was analyzed with a mathematical model derived from data obtained from single sections. The results of this analysis suggested that at least 93–99% of lymphocytes (within 90% limits of confidence) take an intercellular path in their migration from blood to lymph.

It is concluded that lymphocytes migrate across the vascular endothelium by insinuating themselves between endothelial cells and not by passing through them. Rather than constituting an increased barrier to cell migration, the unusual height of the endothelial cells in these vessels is interpreted to be a special adaptation which allows sustained cell traffic without excessive fluid loss taking place concomitantly.
THE HURLER SYNDROME: A STUDY OF CULTURED LYMPHOID CELL LINES
Authors: Danes B. Shannon , Hütteroth T. H. , Cleve H. , Bearn Alexander G.
Published: June 2004

Lymphoid suspension lines have been established from three patients with the Hurler syndrome and four normals. The Hurler lines can be distinguished from normals by (a) staining characteristics, (b) increase in total cellular mucopolysaccharide content, and (c) increase in dermatan sulfate. Hyaluronic acid is absent in cultured lymphoid cells from normal persons and patients with the Hurler syndrome. The availability of biochemically marked suspension cultures should prove useful for enzymatic studies as well as for further elucidation of this clinical syndrome.
BLOOD MICROCIRCULATION IN THE LYMPH NODE DURING THE PRIMARY IMMUNE RESPONSE
Authors: Herman Peter G. , Yamamoto Itaru , Mellins Harry Z.
Published: June 2004

Microangiography performed after total blood replacement with contrast material provided complete visualization of the vascular structures of the lymph node.

Starting of the 2nd day, there is capillary redistribution throughout the cortex of the lymph node. The previously rather avascular nodules dissolve, and the cortical lymphoid tissue becomes uniformly vascular. Beginning on the 2nd day and reaching its peak on the 5th day, there is a significant increase in diameter and density of the subcapsular and medullary cord capillaries. 15 days after the antigenic stimulus, the appearance of the microvasculature returns to normal.

The postcapillary venules (the microvascular structures which follow the capillaries) are widely distributed throughout. Histologically, only a fraction of these venules have a high endothelial lining (HE venules). Therefore, it is suggested that among the postcapillary venules, those with high endothelial lining should be specifically denoted. Great individual variation in the number of HE venules was observed, and no correlation with the timing of the immune response could be established.

Whether the microvascular changes described lead to cellular change or are mere expressions of it cannot definitely be stated. However, the significant hypervascularity along the intranodal lymph pathways and the diffuse, even redistribution of the capillaries and postcapillary structures could greatly facilitate the humoral and cellular exchange between the circulating blood, the circulating lymph, and the tissues of the lymph node.
INITIATION OF ANTIBODY RESPONSES BY DIFFERENT CLASSES OF LYMPHOCYTES
Authors: Strober Samuel
Published: June 2004

The life-span and migratory characteristics of rat thoracic duct cells which initiate the adoptive primary and secondary antibody response to diphtheria toxoid (DT) and horse spleen ferritin (HSF) were investigated. The experimental results show that thoracic duct lymphocytes from normal (unimmunized) donors are able to restore the adoptive response of irradiated hosts to HSF. Thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed a marked reduction in their restorative action as compared with unpassaged cells. In addition, the restorative action of cells from donors treated with thymidine-3H for 48 hr before cannulation of the thoracic duct was markedly decreased. This indicates that a population of lymphocytes involved in the adoptive primary response is unable to recirculate from the blood to the lymph and is turning over rapidly (short lived). The nonrecirculating, short-lived lymphocytes are proably "B" cells, since a combination of spleen cells from neonatally thymectomized rats and passaged or thymidine-3H-treated cells restores a vigorous response to HSF.

On the other hand, passaged or thymidine-3H-treated thoracic duct cells from donors immunized to DT or HSF are able to restore a vigorous adoptive secondary antibody response. Experiments with the hapten-protein conjugate, DNP-DT, show that the majority of both helper ("T") and precursor ("B") cells are able to recirculate and are slowly turning over (long lived). The findings suggest that T lymphocytes involved in both the primary and secondary antibody response are recirculating, long-lived cells. However, B lymphocytes involved in the primary response are nonrecirculating, short-lived cells ("B1" cells) which undergo a fundamental physiological change to recirculating, long-lived cells ("B2" cells) involved in the secondary antibody response.