bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation Immunology of the Anterior Chamber of the Eye
Authors: Kaplan Henry J. , Stevens Thomas R. , Streilein J. Wayne
Published: December 2022

A graft-vs-host reaction (GVHR) expressed as an anterior uveitis was elicited within the anterior chambers of the eyes of F1 hybrid rats by the inoculation of suspensions of allogeneic, parental lymph node cells. This response resembled local GVHRs induced in other sites, except for the failure of refractoriness to appear following resolution of the acute phase. Because lymphoid cells within the anterior chamber have been shown to leave and make an impact on the systemic immunologic apparatus of the recipient, rather than remain isolated within the eye, it was suggested that the vascular route by which these cells disseminate is an important determinant of whether refractoriness will ensue from a local GVHR.
Transplantation Immunology of the Anterior Chamber of the Eye
Authors: Kaplan Henry J. , Streilein J. Wayne , Stevens Thomas R.
Published: December 2022

The mechanism by which the anterior chamber of the eye extends immunologic privilege to allogeneic donor tissues has been studied in inbred rats. Inoculation of allogeneic lymphoid cells into the anterior chamber demonstrated that although the site lacks a lymphatic drainage, the afferent limb of the immunologic reflex are is intact because the recipient can recognize and mount a specific immune response. In addition, host immunity was able to express itself within the anterior chamber when induced systemically, indicating that the efferent limb of the reflex arc is also intact. Therefore, it is suggested that the unique immunologic features of the anterior chamber may result from the obligate intravenous presentation of graft antigen to the host's systemic immunologic apparatus, a route that prejudices the host's response in the direction of tolerance and/or enhancement rather than cell-mediated, tissue destructive immunity.
Modulation of HL-A Antigens by Anti-HLA Antiserum: Effects on the Cytotoxicity Assay and Mixed Leukocyte Reaction
Authors: Sadeghee Saeed , Hebert Jacques , Kelley Joan , Abdou Nabih I.
Published: December 2022

Modulation of human leukocyte antigen (HLA) was attempted by treating leukocytes with specific anti-HLA antiserum or by their passage through columns coated with anti-HLA or a double layer of HLA-anti-HLA. The modulated cells were resistant to the cytotoxic effects of the anti-HLA, and they were poor stimulators and good responders to allogeneic cells in the unidirectional mixed leukocyte reaction. Modulated cells regained their HLA 16 hr after modulation if kept in cell suspension alone. The proliferative responses of modulated cells to mitogens were as good as non-modulated cells, indicating that modulation was probably not caused by depletion of lymphoid cells. Supernatants of modulated cells that were incubated over-night or preformed HLA-anti-HLA complexes were capable of suppressing and enhancing the MLR of specific cells depending on the dose used. The similarities of modulation of HLA to other lymphocyte receptors and the limitation of application of the modulation phenomenon to transplantation of allogeneic cells are discussed.
Studies on Lymphokines: The Production of Antibody to Guinea Pig Lymphotoxin and its Use to Distinguish Lymphotoxin from Migration Inhibitory Factor and Mitogenic Factor
Authors: Gately Maurice K. , Gately Celia L. , Henney Christopher S. , Mayer Manfred M.
Published: December 2022

Guinea pig lymphotoxin, which was produced by stimulating immune lymph node cells with the specific antigen, ovalbumin, was partially purified by the sequential use of Pevikon block electrophoresis, ion exchange chromatography on DEAE-cellulose, and polyacrylamide disc gel electrophoresis. The lymphotoxin recovered from the final step was purified approximately 200- to 300-fold as compared to the starting material, but nevertheless contained at least one major contaminant protein. Rabbits were immunized with the partially purified lymphotoxin, and an antiserum capable of neutralizing the cytotoxic effect of lymphotoxin was obtained. The anti-lymphotoxin activity was shown to be due predominantly to IgM immunoglobulin. The antiserum neutralized concanavalin A-induced lymphotoxin with equal efficiency as antigen-induced lymphotoxin. On the other hand, the anti-lymphotoxin serum did not neutralize preformed mitogenic factor or migration inhibitory factor (MIF) which had been produced by antigen-stimulated immune lymph node cells. Thus these activities appear to be due to substances which are antigenically distinct from lymphotoxin. Likewise, anti-lymphotoxin serum, when present in cultures of antigen-stimulated immune lymphoid cells, caused no diminution in the amount of mitogenic factor or MIF which was produced, indicating that it had no direct deleterious effect on the function of the lymphoid cells responsible for producing these lymphokines.
Depression of in Vitro Responsiveness to Phytohemagglutinin in Spleen Cells Cultured from Chickens with Marek's Disease
Authors: Theis Gail A. , McBride Raymond A. , Schierman Louis W.
Published: December 2022

Cultures of dispersed spleen cells, prepared from MDV-infected chickens with MD visceral lymphomas, showed marked depression of responsiveness to the T cell mitogen PHA, as measured by 3H-Tdr incorporation in cells in vitro. When data are expressed quantitatively in terms of cpm/105 viable cells, the functional depletion of PHA-responsive cells appears to result from lower levels of 3H-Tdr incorporation in the PHA-stimulated spleen cultures from chickens with acute MD symptoms, as compared to similar cultures from uninfected isolator-reared control chickens. It is suggested that depression of PHA-induced blastogenesis in spleen cell cultures from chickens with acute MD reflects virus-related alterations in T lymphocytes.
Differentiating Feline T and B Lymphocytes by Rosette Formation
Authors: Taylor Diane , Hokama Y. , Perri S. F.
Published: December 2022

The number of bone marrow-derived and thymus-dependent lymphocytes in the peripheral blood of felines was assessed. Feline bone marrow-derived lymphocytes were determined by erythrocyte antibody complement (EAC)-rosette formation and membrane immunofluorescence. A good correlation was observed between the cells forming EAC-rosettes (mean of 40.2 ± 9.7%) and those possessing membrane immunoglobulins (mean of 45.3 ± 4.1%).

Feline thymus-dependent lymphocytes form non-immune (E)-rosettes with rodent erythrocytes (mouse, rat, guinea pig) but not with erythrocytes from humans, monkeys, dogs, mongooses, chickens, rabbits, sheep, and hamsters. An average of 32.3 ± 9.2% of the peripheral blood lymphocytes of cats formed rosettes with guinea pig erythrocytes. Antibody blocking, cytotoxicity, and mix-rosette studies demonstrated that guinea pig red blood cells bind specifically to T lymphocytes. Of feline peripheral blood lymphocytes, 41.0 ± 7.5% showed fluorescent staining with fluorescein-labeled rabbit anti-cat thymus antiserum.
Immunologic Effects of Morphine Administration in Rabbits
Authors: Ringle David A. , Herndon Betty L.
Published: December 2022

Long-term effects of morphine administration on immunologic test responses were studied in female rabbits. Implantation of morphine-containing pellets was found to be more effective than injection of morphine sulfate solutions in promoting increased serum binding of 14C-morphine. A large part of the increased morphine binding by sera associated with administration of morphine was found in serum fractions containing γ-globulin and was absent in γ-globulin-free fractions. These sera showed some degree of specificity for the morphine configuration in tests with other narcotics. They also gave positive immunologic test reactions in passive hemagglutination and radial immunodiffusion tests involving serum albumins conjugated with morphine derivatives. Other evidence for immunologic responsiveness against morphine by morphine-pretreated rabbits was shown by cutaneous hypersensitivity reactions against morphine-carrier conjugates and by a diminution of the serum morphine-binding response in rabbits given an immunosuppressive dose of cyclophosphamide. Failure of naloxone, a morphine antagonist, to alter the serum morphine-binding response suggested that serum levels of the morphine-binding globulin studied here were not directly related to morphine withdrawal.
Mouse Effector Functions Involved in the Antibody-Dependent Cellular Cytotoxicity to Xenogeneic Erythrocytes
Authors: Cohen Stefan A. , Ehrke M. Jane , Mihich Enrico
Published: December 2022

Mouse spleen cell populations were fractionated by carbonyl iron depletion and nylon wool column separation. The fractions were tested for phagocytic and lytic activity against antibody-coated 51Cr-labeled sheep red blood cells. Carbonyl iron resistant cells had no phagocytic activity but caused lysis at a relatively slow rate. Nylon wool column nonadherent cells had a similar effect. In contrast with the slow lytic action of these cells, nylon wool adherent cells or non-carbonyl iron-treated cells had phagocytic as well as rapid lytic action. Under the conditions studied, both rapid and slow lytic functions were saturable whereas the phagocytic function was not.
Analysis of an HL-A Antiserum by Iso-Electric Focusing
Authors: Reisner Emily G. , Reisner Howard M. , Chung K. S. Su , Folds James D. , Amos D. Bernard
Published: December 2022

An anti-HL-A 3 antiserum with cross-reacting activity for HL-A 1 and HL-A 11 was subjected to isoelectric focusing over a pH 5–8 gradient. The cytotoxic activity of the serum focused into three distinct peaks, one at the basic end of the gradient, one between pH 6 and pH 7 and one at the acidic end. The first and second peaks reacted with HL-A 3 positive cells and HL-A 3 negative cells positive for cross-reacting antigens. The third peak reacted only with HL-A 3 positive cells.
The Antibody Responses to Myelin Basic Protein (BP) in Lewis Rats: The Effects of Bordetella Pertussis
Authors: Pitts Olin M. , Varitek Vincent A. , Day Eugene D.
Published: December 2022

A time-course study was made of the systemic humoral immune response of Lewis rats to myelin basic protein (BP) as influenced by the dosage of ancillary pertussis adjuvant. Peak activities were observed 5 to 7 weeks after injection. When injected proximal to BP and Mycobacterium butyricum in complete Freund's adjuvant (CFA), Bordetella pertussis at the level of 4 billion organisms doubled the antibody-binding activity of rat sera for 125I-labeled BP as compared to activities obtained with 0, 2, 6, or 8 billion. The severity of clinical symptoms of experimental allergic encephalomyelitis (EAE) at the end of the 2nd week was greatest in rats receiving 64 billion organisms, the very same rats that displayed a severely dampened humoral immune response to BP 5 weeks later. When pertussis was injected i.p. rather than proximal to the CFA mixture, the time-course of the humoral immune response displayed a different profile—unusually high binding activities at the time of onset of EAE that fluctuated back and forth from high to low and that eventually dampened to an intermediate level.
The Influence of Foster Nursing on the Survival and Immunologic Competence of Mice and Rats
Authors: Silvers Willys K. , Poole Timothy W.
Published: December 2022

A series of experiments were undertaken in mice and rats to confirm the report that foster nursing rats of one strain, on mothers of a different strain, can influence their survival and immunologic competence as a consequence of their receiving a significant number of immunologically competent leukocytes via the milk. These experiments have included foster nursing mice and rats, either immediately after birth, or when 25 to 36 hr old, on H-2 incompatible and Ag-B compatible and incompatible mothers, respectively, and challenging them with ear skin grafts of the same genotype as their surrogate mother. They also have included fostering animals rendered tolerant of their surrogate mother's transplantation antigens. In no instance was any evidence obtained that foster nursing can prejudice the survival or influence the immunologic competence of mice or rats.
A Subpopulation of T Cells Bearing Fc Receptors
Authors: Basten Antony , Miller J. F. A. P. , Warner Noel L. , Abraham Robert , Chia Eunice , Gamble Jennifer
Published: December 2022

A wide range of cell populations were examined for Fc receptor (FcR)-bearing T cells: thymus, spleen, peritoneal cells, and T cells activated to H-2 antigens in spleen (ATC spleen) and in thoracic duct lymph (T-TDL). In addition, B lymphocytes from thoracic duct lymph of athymic nude mice and a Thy-1-positive, FcR-positive thymoma served as control cell populations. Reagents used were aggregates of human γ-globulin and of various mouse myeloma proteins (IgG1, IgG2a, IgG2b), radioiodinated antigen-antibody complexes, and sheep erythrocyte antibody rosettes. Labeling techniques involving radioautography and immuno-fluorescence were used to demonstrate FcR by one of the above reagents and to identify T cells either by staining with anti-Thy-1.2 or by a specific rabbit anti-mouse T cell serum, or by failure to stain with anti-mouse immunoglobulin. In some experiments phagocytic cells were removed whereas in others they were identified by their capacity to engulf latex particles. Approximately 25% of cells with T cell markers were FcR-bearing cells in thymus, normal spleen, and peritoneal cavity, and 17% in ATC spleen. FcR on T cells in peripheral lymphoid tissues were detectable by aggregates of HGG and myeloma proteins and by radioiodinated immune complexes. Those on T cells in thymus were revealed only by aggregates of HGG. Circulating T cells (T.TDL) failed to display FcR: a) despite the use of a wide range of the above labeling techniques, each of which was shown to detect FcR on other T cells, thymoma cells, and B cells, and b) even after removal of Ig associated with their cell membranes. In contrast to B cell FcR which bound IgG1 preferentially, those on T cells bound both IgG1 and IgG2, raising the possibility that the FcR on T cell is distinct from that on B cell. It is concluded that FcR-bearing T cells represent a subpopulation of cells within the thymus and the secondary lymphoid tissues.
Carrier Specificity vs Hapten Specificity in Classical Cell-Mediated Contact Sensitivity to Dinitrochlorobenzene
Authors: Levis William R. , Powell John A. , Whalen John J.
Published: December 2022

An anti-HL-A human alloantiserum contained antibodies specific for B lymphocyte alloantigen(s). These antigens were distinct from HL-A antigens and, unlike the latter, were clsely associated with B lymphcoyte Fc receptors. By analogy to the mouse, we suggest that these antigens are associated with an Ir gene region linked to the HL-A locus.
Molecular Restriction of Anti-DNP Antibodies Induced by (DNP)2-Gramicidin S
Authors: Montgomery Paul C. , Rockey John H. , Kahn Ronald L. , Skandera Cheryl A.
Published: December 2022

The molecular properties of anti-DNP antibodies were studied in 80 rabbits hyperimmunized with (DNP)2-gramicidin S. Unimmunized animals or those previously skin-painted with DNFB were subjected to biweekly injections of (DNP)2-gramicidin S. Isoelectric focusing revealed that the spectrotypes of the anti-DNP antibodies fell into three classifications: monoclonal, 18 to 21%; biclonal, 21 to 30%; and restricted, 14 to 26%. In each immunization protocol 35% of the rabbits did not respond. Longer time periods and more intensive immunization were necessary to achieve an anti-DNP response than with conventional DNP-protein conjugates, with skin painting tending to shorten the overall response time. The anti-DNP responses were invariant with respect to affinity and isoelectric spectra regardless of the immunization protocol or degree of restriction. Chain reassociation studies on antibodies purified from the sera of rabbits displaying monoclonal spectrotypes provide additional evidence that such antibodies are biosynthetically homogeneous. These data support the concept that carrier complexity influences the heterogeneity of the anti-hapten response but strongly suggests that the genetics of an outbred population may be an overriding factor in controlling response heterogeneity.
Studies on the Adjuvant Effect of Bordetella Pertussis Vaccine to Sheep Erythrocytes in the Mouse
Authors: Murgo Anthony J. , Athanassiades Thomas J.
Published: December 2022

The adjuvant effect of Bordetella pertussis vaccine (PV) on the antibody response to sheep erythrocytes (SRBC) has been studied in vitro with the Mishell-Dutton immunization technique. The addition of PV to cultures of spleen cells obtained from normal non-immunized mice markedly enhanced the plaque-forming cell response to SRBC. The greatest enhancement was evident at 24 hr of culture. PV was also shown to enhance the antibody response of spleen cells that had been depleted of either T lymphocytes or adherent cells, presumably macrophages. In addition, it was found that PV, per se, released into the culture medium a soluble cell-free component(s) that contributed significantly to adjuvanticity. The results suggest that at least one of the ways that PV enhances the in vitro immune response to SRBC is by direct stimulation of precursors of antibody-forming cells.
Reactivity of Rabbit Antiserum to Guinea Pig Eosinophils
Authors: Gleich Gerald J. , Loegering David A. , Olson Gail M.
Published: December 2022

Although the eosinophil has been recognized as a distinctive cell type for almost 100 years, the major functions of these cells remain unknown. As an approach to defining these functions we have treated guinea pigs with rabbit antiserum to eosinophils (AES) in an attempt to ablate these cells from tissues. Rabbits were immunized thrice with purified eosinophils and the antisera were absorbed with peripheral blood cells from guinea pigs made eosinopenic with methyprednisolone to remove antibodies reactive with serum proteins and erythrocytes. The resulting sera reacted strongly with eosinophils in cytotoxicity tests and had weak or no reactivity with neutrophils. However, absorption of AES with purified neutrophils removed anti-eosinophil activity. Intraperitoneal injection of potent AES into guinea pigs resulted in complete absence of eosinophils from the peripheral blood and from the peritoneal cavity with only transient or no reduction in circulating neutrophils. Eosinophils were also reduced in bone marrow, spleen, and intestine. The ability of neutrophils to absorb AES activity in spite of weak reactivity in cytotoxicity tests may reflect a quantitative difference in antigenic determinants between eosinophils and neutrophils.
The Properties of Plaque-Forming Cells from Autoimmune and Normal Strains of Mice with Specificity for Autologous Erythrocyte Antigens
Authors: Lord Edith M. , Dutton Richard W.
Published: December 2022

Treatment of mouse erythrocytes with the proteolytic enzyme, bromelain, reveals antigenic determinants not normally exposed on the erythrocyte surface. It was found that not only NZB mice, a known autoimmune strain, but also several normal strains of mice contain cells in small numbers in their spleens and in larger numbers in their peritoneal cavities which will form plaques against bromelain-treated MRBC. During in vitro culture the number of anti-BR-MRBC PFC increases slightly in the spleen cell populations whereas the number of these PFC in peritoneal cells increases dramatically to as many as 10,000 PFC/106 cells. The plaques detected in this assay contain a central lymphoid cell and their development, which requires the presence of complement and protein synthesis, is inhibited by anti-mouse immunoglobulin.
B Lymphocyte Differentiation from Fetal Liver Stem Cells In89 Sr-Treated Mice
Authors: Kincade Paul W. , Moore Malcolm A. S. , Schlegel Robert A. , Pye John
Published: December 2022

89Sr treatment was used to determine if stem cells in young fetal liver could differentiate to mature B lymphocytes in adult animals that lacked functional bone marrow. Isotope injection alone resulted in a severe and lasting depletion of bone marrow cells and particularly lymphocytes, multipotential stem cells, and progenitors for granulocytes and macrophages. The latter two functional populations of cells expanded in number in the spleen but not the liver after their destruction in bone marrow. The total body content of stem cells did not, however, return to normal. Spleen B cells and lymphocytes lacking B or T cell markers were reduced by 89Sr treatment and possible reasons for this depletion are discussed. B lymphocytes were formed in lethally x-irradiated mice that had less than 1% of normal bone marrow function after reconstitution with fetal liver cells. These cells were immunologically mature by virtue of their ability to mount a primary immune response and function in a thymus-independent adoptive anti-hapten response.
7S Class-Restricted Hapten-Specific Paralysis by Injection of Thymus-Independent Hapten-Carrier Conjugate
Authors: Del Guercio P. , Poirier Marie France , Thobie Nicole
Published: December 2022

The shift from IgM anti-hapten antibody production to IgG anti-hapten antibody production, subsequent to challenge with a T-dependent conjugate, is inhibited in mice by preimmunization with the T-independent DNP-LE conjugate. The results suggest that DNP on levan triggers off 19S T-independent anti-hapten precursors and paralyzes 7S T-dependent anti-hapten precursors.
Human Chorionic Gonadotropin: Effects of Crude and Purified Preparations on Lymphocyte Responses to Phytohemagglutinin and Allogeneic Stimulation
Authors: Caldwell Joseph L. , Stites Daniel P. , Fudenberg H. Hugh
Published: December 2022

The factors that prevent maternal immunologic rejection of the histoincompatible fetus are not understood. High levels of human chorionic gonadotropin (HCG) are present in the placenta, and several reports have noted suppression of mitogen-induced lymphocyte transformation when cultures were supplemented with crude preparations of HCG. Purified HCG and multiple lots of crude HCG obtained from different suppliers were examined for their ability to suppress lymphocyte transformation produced by phytohemagglutinin (PHA) or allogeneic stimulation. Crude preparations of HCG produced suppression of the lymphocyte stimulation induced by low doses of PHA, but the suppression could be overcome completely by increasing the PHA dose. The purified preparations of HCG produced no suppression of lymphocyte responses, even at the lower PHA dose. Purified HCG did not give a dose-related suppression of allogeneic lymphocyte responses, and crude lots of HCG gave highly variable results. One lot of crude HCG produced spontaneous stimulation of lymphocytes. Isoelectric focusing of HCG preparations demonstrated multiple bands, and lymphocyte suppression may be secondary to these additional unidentified proteins. The failure of purified HCG to suppress lymphocyte responses makes it unlikely that the absence of maternal rejection of the fetus is due to high placental levels of HCG.
Immune Response to a Syngeneic Mammary Adenocarcinoma
Authors: Kuperman Oded , Fortner G. William , Lucas Zoltan J.
Published: December 2022

A method is described for the consistent in vitro generation of cytotoxic cells by incubating Fischer 344 rat spleen cells on monolayers of a syngeneic mammary adenocarcinoma. Significant cytotoxicity by in vitro culture is generated as early as 3 days after initiation and effector cells are cytolytic only toward target cells of the sensitizing monolayer. Reciprocal sensitization with allogeneic fibroblasts as the immunizing monolayer yielded effector cells cytolytic for the fibroblasts but without effect on the mammary tumor. The consistency in the generation of cytotoxic cells by in vitro culture should permit its standardized use in following other related immune phenomena such as blocking by serologic factors and suppression, recruitment or memory for cytotoxic function.
Number of Histocompatibility Loci in Syrian Hamsters
Authors: Silvers Willys K. , Gasser David L. , Murphy Michael R.
Published: December 2022

Syrian hamsters descended from animals captured in the summer of 1971 have been utilized to obtain some estimate of the number of histocompatibility loci in this species. The survival of skin grafts on two F2 populations derived from these animals and two isogenic stocks indicates considerably more histocompatibility loci than previously reported.
The Humoral Response of Mouse Spleen Cells to Two Types of Sheep Erythrocytes
Authors: McCarthy Margaret M. , Dutton Richard W.
Published: December 2022

Some strains of mice discriminate between two types of sheep erythrocytes (H or L-SRBC) and others do not. It is proposed that there are shared antigen(s) common to both H and L and extra antigen(s) present only in H. It is shown that individual clones of antibody-forming cells make antibody to either the shared or extra antigens. These antigenic differences are not found to correlate with any of the known major sheep erythrocyte antigens.

The genetic control of the ability to discriminate between these two types of red cell was investigated by an analysis of the response of F1, F2 and backcross mice. The results suggest that the response is under multigene control. BL/6 mice give high responses to the extra antigens and low responses to the shared (high discriminator). DBA/2 gives high responses to the extra antigen (nondiscriminator). F1 mice give high responses to both extra and shared antigen but still discriminate between the two types of erythrocytes (low discriminator). Additional phenotypes appear in the F2 and backcross mice.
B Cells in the Appendix and Other Lymphoid Organs of the Rabbit: Complement Receptor Lymphocytes
Authors: Calkins Catherine E. , Carboni Joan M. , Waksman Byron H.
Published: December 2022

Complement receptor lymphocytes were demonstrated in rabbit lymphoid organs, the spleen containing the highest numbers (35%) and the thymus none. Extremely variable numbers (up to 50%) were detectable in the appendix. B and T cell depletion, rosette depletion, and histologic staining indicate that these CRL are B cells in the rabbit as in other species. The variable behavior of B cells in the appendix suggests a difference between this lymphoid population and those of other rabbit lymphoid organs.
Effects of Migration Inhibiting Factor(s) on the in Vitro Detachment of Macrophages
Authors: Weiss Leonard , Glaves Dorothy
Published: December 2022

Supernatants from spleen cells, derived from mice injected with BCG and cultured with PPD, specifically inhibited the migration of normal mouse peritoneal macrophages when compared with control supernatants. Migration inhibitory supernatants were also shown to decrease the detachment of adherent macrophages in a novel test system. Both macrophage migration and detachment inhibitory activities were abrogated by neuraminidase and chymotrypsin treatment of supernatants but were thermostable, suggesting that the detachment test is a sensitive index of MIF activity.
In Vitro Immunogenicity of Trinitrophenylated Bacteriophage T4
Authors: Jennings John J. , Baltz Marilyn , Rittenberg Marvin B.
Published: December 2022

A primary immune response was obtained in vitro to trinitrophenylated bacteriophate T4 (TNP-T4) by using normal BALB/c spleen cells challenged in vitro. The primary response was limited to anti-TNP; we failed to find evidence of a primary anti-T4 response in spleen cell cultures challenged with either TNP-T4 or native T4. In vivo priming with the carrier T4 failed to enhance the subsequent in vitro response to TNP-T4 although such priming sometimes caused suppression of the anti-hapten response. The addition of excess free carrier to spleen cell cultures challenged with TNP-T4 failed to suppress the anti-TNP response. Spleen cells treated with anti-θ plus complement were unaffected in their ability to respond to TNP-T4. We conclude that TNP-T4 should be classified among the thymus independent antigens.
Studies of Thymic Factors
Authors: Gershwin M. Eric , Steinberg Alfred D. , Woody James N. , Ahmed Aftab
Published: December 2022

The restoration of sensitivity to azathioprine of athymic (nu/nu) mouse splenic rosette-forming cells (RFC) has been used by others to assay thymic hormone. These previous studies have led to the conclusion that a major factor in the development of autoimmunity in New Zealand (NZ) mice and patients with systemic lupus erythematosus (SLE) is the premature loss of thymic hormone. We have studied the mouse rosette assay and find that poly A Poly U and single stranded DNA, in addition to thymosin, restored azathioprine sensitivity to nu/nu RFC. Thus, other substances may mimic thymic hormone, perhaps via the cyclic AMP system. Furthermore, antibodies to T cells were found to interfere with the assay. Sera from old NZ mice which contain naturally occurring thymocytotoxic antibodies (NTA) failed to restore azathioprine sensitivity. Small quantities of NTA prevented normal sera from functioning in the assay. We conclude that the role of thymic hormone(s) in the development of autoimmunity in NZ mice and patients with SLE must be completely reevaluated.
Cationic Proteins of Human Granulocytes
Authors: Venge Per , Olsson Inge
Published: December 2022

The chymotrypsin-like cationic proteins of human granulocytes are shown to possess the ability to produce conversion of the complement components C1s, C4, C3, and C5 as detected by crossed immuno-electrophoresis. This ability seems to be a direct proteolytic effect. Incubation of cationic proteins with serum or functionally pure preparations of C3 and C5 is shown to generate the formation of chemotactic activity which is abolished by prolonged incubation. Also, the chemotactic activity of porcine C5a or spontaneously activated C5 is abolished by incubation with cationic proteins. It is suggested that the chymotrypsin-like cationic proteins of human granulocytes after extrusion from the phagocytic cell play an important role for generation of inflammatory mediators.
Genetic Control of the Murine Cell-Mediated Immune Response in Vivo
Authors: Davis Stephen , Shearer Gene M. , Mozes Edna , Sela Michael
Published: December 2022

Cell-mediated immunity in response to (T,G)-A--L was studied with a radioisotopic footpad assay. It appears that in vivo cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was demonstrated previously for specific antibody synthesis. Evidence is presented in this report which indicates that the cell-mediated immunity measured is a function of a population of T cells.

The apparent controversy between results obtained by analyzing antibody formation and cell-mediated immunity can be explained by assuming the need for cell cooperation between helper T cell and effector T cell, because efficient purely cellular immunity is analogous to T-B cell cooperation needed for antibody production.
Cyanate as an Inactivator of Complement Proteins
Authors: Schultz Duane R. , Arnold Patricia I.
Published: December 2022

Sodium cyanate added to normal human serum or serum from patients with sickle-cell disease resulted in the functional inactivation of C3, C5, C6, C7, and the C3b inactivator, but not C8 and C9. Final concentrations as low as 0.5 mM in serum caused inactivation of 12 to 64% of the C3 after 8 hr at 37°C. The activity of the inactivated C3, C5, and C3b inactivator was not restored by dialysis. Most of the functional activity of C3 in cyanate-treated sera was destroyed by very small quantities of 14C-labeled cyanate that was bound to the protein. C3 inactivation by cyanate occurred in heated sera (50°C, 30 min) and sera treated with EDTA, probably indicating that one mechanism for inactivation was by a direct carbamylation reaction. Both C3 and C5 showed two anodal-migrating forms in two dimensional antigen-antibody crossed electrophoresis in some sera treated with low concentrations of cyanate.

Measurements of circular dichroism of highly purified carbamylated C3 showed no detectable changes in structure even though most of the functional activity was destroyed. Purified, inactive C3 that was carbamylated with 14C-labeled cyanate was capable of binding to EAC142, but the resulting EAC1423 was weakly positive for immune adherence and negative for agglutination with anti-C3 antiserum. Unlabeled, cell-bound C3b on EAC142 was not susceptible to cyanate action as shown by no loss in immune adherence and positive agglutination with anti-C3 antiserum. The C3b inactivator was more susceptible to cyanate than C3 in a short time period, whereas both were inactivated after 8 hr.

Since cyanate is currently being evaluated as a treatment for sickle-cell disease, the inactivation of C3 by the drug is an important consideration for such patients who are already deficient in C3 dependent heat-labile opsonins that aid in host defense.
EAC4 and EAC14 Production Without Purified C1
Authors: Linscott William D.
Published: December 2022

EAC4 and EAC14 of high activity were prepared by treating sensitized red cells with human or guinea pig serum in the presence of TTHA, a chelating agent which binds Mg++ more firmly than Ca++. The reaction was carried out at 0°C and at low pH to maximize C1 and C4 activity and to minimize C3 contamination. Cells prepared with guinea pig complement were contaminated with C2, which could be decayed away at 37°C. Cells sensitized with IgG antibody were more reactive than those sensitized with whole serum or with IgM, and preparations made with TTHA-complement were more reactive than those prepared with purified C1 plus EDTA-complement. EAC14 stored at 0°C for 3 weeks lost very little activity.
Preparation and Properties of an Antiplasma Cell Serum Directed Against A Defined Plasmacytoma Cell Population
Authors: Lutz Proctor Mary , Herscowitz Herbert B.
Published: December 2022

Heterologous antisera were prepared against a subpopulation of MOPC-104E tumor cells obtained by centrifugation on discontinuous BSA gradients as well as against cells from the whole tumor mass. The gradient-separated cells were more effective than the cells from the whole tumor mass in eliciting antisera not only of higher titer, but also with greater specificity for plasmacytoma antigens. The unabsorbed antiserum prepared against the gradient-separated plasmacytoma population was cytotoxic for murine lymphoid cells, but not for murine kidney, liver, or brain cells. After in vitro absorption with murine thymocytes and removal of anti-immunoglobulin activity by affinity chromatography, the antiserum was found to be reactive against plasmacytoma cells, but was no longer cytotoxic for murine thymus or unstimulated spleen cells. This absorbed antiserum was also cytotoxic for LPS-, but not PHA- or Con A-stimulated normal murine spleen cells.
Desensitization: Effects on Cutaneous and Peritoneal Manifestations of Delayed Hypersensitivity in Relation to Lymphokine Production
Authors: Sonozaki Hidekichi , Papermaster Vera , Yoshida Takeshi , Cohen Stanley
Published: December 2022

Guinea pigs exhibiting delayed hypersensitivity may be desensitized by a single large dose of antigen administered intramuscularly. In the present experiments, desensitization with a soluble protein such as egg albumin (EA) or bovine γ-globulin (BGG) was nonspecific in that they suppressed both cutaneous reactivity and the macrophage disappearance reaction (MDR) to unrelated antigen in doubly immunized animals. In contrast, mycobacterial antigen, at the dose studied, showed limited specificity in that it could suppress the MDR but not a skin test to an unrelated antigen.

Induction of an MDR was shown to be associated with the appearance of macrophage migration inhibitory factor (MIF) and chemotactic activity in the peritoneal exudate fluid. Pretreatment with desensitizing doses of mycobacteria prevented the EA-induced appearance of MIF in the peritoneal fluids. In contrast, chemotactic activity could still be recovered, even though the MDR was suppressed. Mycobacteria functioned as a specific desensitizer not only with respect to cutaneous reactivity, as stated above, but also with respect to the production of chemotactic factor by peritoneal exudate cells. In contrast, mycobacteria functioned as a nonspecific desensitizer with respect to both the MDR and MIF production.

These results suggest that the MDR may be an in vivo manifestation of MIF activity, whereas the cutaneous delayed hypersensitivity reaction may be more dependent upon chemotactic activity.

These observations reported here, taken in conjunction with previously described in vitro studies, suggest that desensitization is a complex phenomenon which may be the result of several different mechanisms acting separately or in concert. The apparent discrepancies in the literature as to whether or not desensitization is a specific process would appear to arise from differences in the experimental model and the particular antigen used.
Interrelationships of Surface Immunoglobulin and Fc Receptors on Mouse B Lymphocytes
Authors: Abbas Abul K. , Unanue Emil R.
Published: December 2022

Receptors for the Fc portion of immunoglobulin (Ig) molecules have been detected on mouse B lymphocytes by an immunofluorescence technique, employing immune complexes of fluorescein-conjugated KLH and rabbit anti-KLH antibody. At 37°C, membrane-bound complexes rapidly undergo capping and clearing from the surface. Modulation of Fc receptors does not alter the amount of distribution of surface Ig, indicating that these two molecules are independent moieties. However, capping of surface Ig by intact or pepsin-digested anti-Ig antibody leads to co-capping of Fc receptors. These results suggest that ligand binding to surface Ig induces some alteration which allows the Ig to enter into an association with Fc receptors.
An Eosinophil Chemotactic Factor Present in Blister Fluids of Bullous Pemphigoid Patients
Authors: Baba Toru , Sonozaki Hidehicki , Seki Kenjiro , Uchiyama Mitsuaki , Ikesawa Yoshiro , Torisu Motomichi
Published: December 2022

Tissue eosinophilia is often found in the inflammatory lesions of bullous pemphigoid. A study made on naturally occurring eosinophil chemotactic activity in the blister fluids of four bullous pemphigoid patients revealed the existence of this activity in all of them. Sephadex G-25 column chromatography showed that the greater part of this eosinophil chemotactic activity was composed of low molecular substance of which the molecular weight was close to that of vitamin B12 (m.w. 1357).

The blister fluids and the sera of these patients contained elevated levels of IgE. An IgE anti-skin basement membrane antibody was found in two of the four sera, and deposits of IgE were detected along the basement membrane zone of the involved skin in one of the patients.

On the basis of these findings, we have reason to believe that an eosinophil chemotactic factor of anaphylaxis (ECF-A) participates in the accumulation of eosinophils in the lesions of bullous pemphigoid.
Heavy Chain Variable Region Allotypic Sub-Specificities of Rabbit Immunoglobulins
Authors: Horng Wayne J. , Knight Katherine L. , Dray Sheldon
Published: December 2022

Four anti-a1 Ab subpopulations were isolated from an anti-a1 antiserum by sequential immunoadsorption chromatography. These four anti-a1 Ab subpopulations were differentially bound by two “limited heterogeneity” Abs having different components of the a1 allotypic specificity. Each of the four anti-a1 Ab subpopulations reacted with a1 IgG molecules obtained from several different a1 rabbits, but not with IgG obtained from a2 and a3 rabbits. A subpopulation designated anti-a1-A Ab reacted with 100% of a1 IgG molecules. Thus, the anti-a1-A Ab recognizes a1 determinants common to all a1 IgG molecules. Each of the other three subpopulations, designated anti-a1-B Ab, anti-a1-C Ab, and anti-a1-D Ab, and anti-a1-D Ab, reacted with only a fraction of the a1 IgG molecules but the sum of the percentages of a1 IgG molecules which reacted with each of these three anti-a1 Ab subpopulations approximated 100% of the a1 IgG molecules. Thus, each of the anti-a1-B Ab, anti-a1-C Ab, and anti-a1-D Ab recognizes non-common determinants distinct for each of three subpopulations of a1 IgG molecules.

Although 65 to 90% of IgG molecules in a1 homozygous rabbits have the a1 allotypic specificity, these IgG molecules are heterogeneous with respect to their antigenic determinants comprising the a1 allotype; at least three kinds of a1 IgG molecules are identified. This heterogeneity probably reflects variation in the amino acid sequence of the VH region of a1 IgG molecules and, therefore, poses a similar argument which had led to the hypothesis of two genes for one polypeptide chain and to the theory of episomal insertions for the genetic control of immunoglobulin synthesis.
Cell-Mediated Immune Response to Mumps Virus Infection in Man
Authors: Chiba Yasuo , Dzierba Judith L. , Morag Abraham , Ogra Pearay L.
Published: December 2022

The antibody and cell-mediated immune response to mumps virus infection was studied in groups of subjects after naturally acquired mumps virus infection, after parenteral immunization with liver attenuated mumps vaccine, and in a population of mumps seronegative subjects. The technique of neutralization of tissue culture infectivity was utilized to study mumps specific antibody. The cell-mediated immunity (CMI) was detected by specific immune release (SIR) of radioactivity by purified lymphocytes after they were reacted with radioactive chromium (51Cr) labeled human conjunctival cell cultures chronically infected with mumps virus. No SIR activity was observed in lymphocytes obtained from cored blood and young individuals seronegative for antibody to mumps virus. Detectable SIR activity was observed in a few older seronegative subjects; however, immunization with mumps vaccine in such antibody negative subjects failed to result in the development of any antibody response in the serum. High SIR activity was observed in the lymphocytes of naturally infected and vaccinated subjects. Although all naturally infected or immunized subjects had varying levels of mumps specific antibody activity in the serum, no correlation existed between the levels of antibody and SIR activity. These observations suggest the development of mumps specific in vitro correlates of CMI after naturally acquired or vaccine-induced mumps virus infection.
Suppression and Reversal of Allergic Encephalomyelitis in Guinea Pigs with a Non-Encephalitogenic Analogue of the Tryptophan Region of the Myelin Basic Protein
Authors: Hashim George A. , Sharpe Richard D. , Carvalho Evelyn F. , Stevens Lawrence E.
Published: December 2022

The administration of synthetic peptide S42 leads to suppression and reversal of experimental allergic encephalomyelitis (EAE) induced in guinea pigs by myelin basic protein. Peptide S42 contains a linear sequence of 21 amino acid residues, H-Phe-Ser-Trp-Gln-Lys-Phe-Ser-Trp-Gln-Lys-Phe-Ser-Trp-Gln-Lys-Phe-Ser-Trp-Gln-Lys-Gly-OH, made up of four repeating unit sequences of H-Phe-Ser-Trp-Gln-Lys-OH in addition to a C-terminal glycine. Injected at relatively high doses, peptide S42 is non-encephalitogenic. It induces delayed-type hypersensitivity which is not followed by EAE, and elicits delayed-type hypersensitivity responses in peptide S42, encephalitogenic tryptophan peptide, or BP-challenged animals for either of the three antigens.

The repeating unit sequence of peptide S42 is analogous to the encephalitogenic tryptophan region of the BP molecule. The sequence homology is responsible for cellular recognition of this antigen by the skin test assay and suggests similar in vivo interaction between peptide S42 and EAE-inducing cells leading to suppression and reversal of disease.
Studies on the Mechanism of Lymphocyte-Mediated Cytolysis
Authors: Plaut Marshall , Bubbers J. Eric , Henney Christopher S.
Published: December 2022

The lysis of allogeneic cells by cytolytically active T lymphocytes has been shown to involve two stages, each with distinct cation requirements. Cytolysis required the presence of Ca++ ions, but addition of Mg++ to Ca++-containing medium synergistically enhanced target cell destruction. This synergistic effect resulted from kinetically separable events mediated by these cations. Thus, optimal adhesions between killer and target cells necessitated the presence of Mg++; interactions also occurred, but less efficiently, in the presence of Ca++. Lymphocyte-target cell interactions resulting from the present of Mg++ did not lead to the lysis of the target cell, until Ca++ were added. A “late” stage of the establishment of a target cell lesion is thus uniquely served by Ca++.
Thymosin Restores T Cell Function and Reduces the Incidence of Amyloid Disease in Casein-Treated Mice
Authors: Scheinberg Morton A. , Goldstein Allan L. , Cathcart Edgar S.
Published: December 2022

Evidence is presented that T cell impairment appears to be specifically related to the pathogenesis of experimental amyloidosis. This conclusion is based on the finding that thymosin administration improves T cell function as measured by mitogen stimulation of spleen cell suspension and at the same time reduces the incidence and severity of amyloid disease in casein-treated mice.
Effect of VHa Locus Allotype-Suppression on the Expression of Closely Linked VHx, VHy, and Cµn Genes in Heterozygous Rabbits
Authors: Kim Byung S. , Gilman-Sachs Alice , Dray Sheldon
Published: December 2022

Injection of a1x-y-n81/a2x32y33n82 heterozygous rabbits at birth with anti-a2 allotype antiserum suppresses the production of the VHa2 gene product a2 Ig as well as the expression of the closely linked Cµn gene product n82 but not of the closely linked VHx and VHy gene products x32 and y33. This effect is related to the appearance of a2 and n82 on the same IgM molecules whereas a2, x32, and y33 appear on different Ig molecules.
Number of Macrophages and Distribution of Mitotic Activity in Regressing and Progressing Moloney Sarcomas
Authors: Russell Stephen W. , Doe William F. , Cochrane Charles G.
Published: December 2022

The concentration of macrophages per gram tumor was as much as five times greater in regressing compared to progressing Moloney sarcomas. Infiltrating mononuclear cells, including macrophages, were closely associated with a cessation of mitotic activity in tumors.
Antibody-Dependent Cell-Mediated Cytotoxicity to Target Cells Infected with Type 1 and Type 2 Herpes Simplex Virus
Authors: Shore Steven L. , Black Charlotte M. , Melewicz Frank M. , Wood Phyllis A. , Nahmias Andre J.
Published: December 2022

The phenomenon of antibody-dependent cell-mediated cytotoxicity (ADCC) has been extended to include target cells acutely infected with herpes simplex type 1 virus (HSV-1) or herpes simplex type 2 virus (HSV-2) in an in vitro system that employs immune human serum and human blood mononuclear cells. The cytotoxic reaction was detectable after 1 hr of incubation and was complete between 4 and 8 hr. The amount of ADCC noted was directly proportional to the logarithm10 of the effector: target cell ratio (E:T), and ADCC was noted at E:T as low as 1:1. The mononuclear effector cell was present in the blood of both HSV immune and non-immune individuals. The immune serum factor was demonstrated to be an antibody with specificity for HSV membrane antigen(s) and was reactive with target cells infected with either of the two HSV types. The antibody rendered the mononuclear cell cytotoxic by sensitization of the target cell rather than by direct attachment to or “arming” of the mononuclear cell. The physiochemical properties of the antibody as well as its presence in cord blood demonstrated that it is an immunoglobulin of the IgG class.