bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen‐specific suppressor cells in hapten‐specific carrier‐determined tolerance
Authors: Aldo‐Benson Marlene A.
Published: February 2007

Tolerance to the hapten 2,4‐dinitrophenyl (DNP) induced by the injection of DNP coupled to isologous IgG (carrier‐determined tolerance) is associated with a receptor blockade of antigen‐binding lymphocytes. In the present study, hapten‐specific suppressor cells were detected in the spleens of mice made tolerant by intravenous injection of 200 μg DNP‐IgG. When spleen cells from mice rendered tolerant to DNP were co‐cultured with normal spleen cells in Marbrook cultures, the response to DNP‐Ficoll was suppressed, while the response to sheep red blood cells was not altered. Depletion of T cells from these spleens restored the normal anti‐DNP response. The suppressor cells were not detectable in the spleen lymphocyte population of mice in the early stages of tolerance but were present on day 7 after injection of tolerogen, and disappeared by day 14. Mice injected with larger doses of 1 mg or four weekly doses of 200 μg DNP‐IgG did not have detectable suppressor cells. Thus, it appears that a short‐lived suppressor T cell is generated in carrier‐determined tolerance. This cell most likely plays a minor role in the mechanism of carrier‐determined tolerance and may be associated with the receptor blockade which is seen early in tolerance.
A novel interaction involving a polypeptide chain (P33) in covalent linkage with IgM on the surface of a Burkitt lymphoma cell line (Daudi)
Authors: Singer Paul A. , Williamson Alan R.
Published: February 2007

The surface IgM of Daudi Burkitt lymphoma cells has been shown to consist of μ chains and x chains covalently linked, by disulfide bonding, to a novel polypeptide chain of approximate molecular weight 33 000. This novel polypeptide chain (P33) is similar in several properties to the heavy chain of the Ia antigen: glycoprotein nature; apparent molecular weight; isoelectric behavior and cysteine content. The linkage of P33 to surface immunoglobulin has not been observed with any other human lymphoma or lymphoblastoid cell lines.
Adrenoreceptors, cyclic nucleotides, and the regulation of spleen cell antigen binding in urodele and anuran amphibians
Authors: Hodgson Ruth M. , Clothier Richard H. , Balls Michael
Published: February 2007

Adults of four anuran amphibian species and five urodele species were immunized with a 25% suspension of horse erythrocytes. After 8 or 14 days, spleen lymphocytes were removed and their specific red cell‐binding capacities tested by immunocytoadherence. Antigen‐binding cells were classified as high‐dose nonsecretory or secretory according to whether they bound a single layer or several layers of erythrocytes. Adrenaline stimulated α and β adrenoreceptors of cells from all four anuran species, giving an α effect (a reduction in rosette formation) in the presence of β antagonists, and a β effect (an increase) in the presence of α antagonists.

Responses similar to α and β adrenergic responses were shown by samples treated with dibutyryl cyclic GMP (db‐cGMP) and dibutyryl cyclic AMP (db‐cAMP), respectively, and added methylxanthines and ionophores also increased rosette formation by Xenopus laevis lymphocytes. Added alone, the antagonists used did not affect rosette formation, and the increase induced by db‐cAMP was not blocked by a β adrenoreceptor antagonist.

The stimulation of a and/or β adrenoreceptors resulted in a reduction in rosette formation by cells from all five urodele species, as did the addition of db‐cGMP. However, in samples from four urodele species, db‐cAMP increased rosette formation. Added db‐cAMP reduced rosette formation by lymphocytes from the fifth urodele species tested, i.e. Triturus cristatus carnifex. The results are discussed in terms of the involvement of surface adrenoreceptors and intracellular mechanisms in the regulation of immune responses, and in terms of the evolution of immune capacity within the Amphibia.
Requirement of parental T lymphocytes for the in vitro induction of F1 hybrid anti‐parent cytotoxicity
Authors: Nakamura Ichiro , Cudkowicz Gustavo
Published: February 2007

Primary F1 anti‐parent cell‐mediated lympholysis (CML) is a specific response generated in mixed cultures by F1 T lymphocytes with the aid of macrophage‐like cells of responder and stimulator type. A model was described in which the induction of this response required T lymphocytes among stimulators, as judged by the lack of induction following T cell depletion of parental cells by (a) separation on nylon wool columns, (b) treatment with anti‐Thy‐1 antiserum and complement, (c) treatment of donor mice with rabbit anti‐mouse thymocyte serum, or (d) congenital absence of the thymus in nu/nu donors. The parental T lymphocytes required were relatively mature, as indicated by resistance to cortisone, persistence after adult thymectomy, and sensitivity to xenogeneic anti‐thymocyte antiserum. T‐deprived cell populations retained the ability to induce allogeneic CML.

Parental lymphoma cells, spleen cells stimulated by mitogens for T or B lymphocytes, normal cells of central and peripheral lymphoid organs, and peritoneal exudate cells, all served to a varying extent as targets for anti‐parent cytotoxic effectors (CTL), but there was no close correlation with their ability to serve as stimulators. Spleen or peritoneal exudate cells of athymic mice were capable of serving as “antigenic” targets for specific F1 anti‐parent CTL, and yet failed to induced the response. Thus, the role of parental T cells in the induction of F1 anti‐parent cytotoxicity was not that of bearing the “antigen”. It was concluded that irradiated parental T lymphocytes provided back stimulation to F1 hybrid responders, either directly or indirectly via the activation of macrophage‐like cells. Under certain circumstances, however, the requirement for parental T cells can be circumvented.
Close association between particular I region‐determined cell surface antigens and Ir gene‐controlled immune responsiveness to synthetic polypeptides in wild rats
Authors: Günther Eberhard
Published: February 2007

The relationship between major histocompatibility complex (MHC) and genetic control of immune responsiveness to the synthetic polypeptides (T, G)‐A–L [poly‐(LTyr,LGlu)‐poly(DLAla)–poly(LLys)] and (H, G)‐A–L [poly(LHis,LGlu)‐poly‐(DLAla)–poly(LLys)] has been studied in 26 wild rats. The major histocompatibility complex (MHC) genotype frequencies observed were not different from those expected according to the Hardy‐Weinberg formula. More than half of the wild rats carried MHC‐linked responder Ir‐TGAL and Ir‐HGAL genes. High or intermediate responsiveness to (T, G)‐A–L and high responsiveness to (H, G)‐A–L were always found to be associated with particular I region‐determined cell surface antigens. These antigens could be identified serologically and by primary and secondary mixed lymphocyte reactions, and were similar or identical to I region products of (T, G)‐A–L high responder or (H, G)‐A–L intermediate responder inbred rat strains. The strong associations between cell surface antigens and immune responsiveness could be due to linkage disequilibrium or to pleiotropy. Since the same I region‐determined cell surface structure could be associated either with high or intermediate anti‐(T, G)‐A–L antibody titers, the presence of the Ia antigen(s) identified did not seem to guarantee high antibody responsiveness to the test antigen.
Functional mosaicism of the lymphocyte plasma membrane. II. Characterization of membrane subtractions of activated thymocytes
Authors: Rode Harold N. , Mähler Bernd , Loracher Alois , Resch Klaus
Published: February 2007

Plasma membranes of thymus lymphocytes can be fractionated by affinity chromatography on concanavalin A (Con A)‐Sepharose into two major fractions: one, MF‐1, elutes freely from the affinity column, the second, MF‐2, adheres specifically to Con A‐Sepharose. The adherent fraction MF‐2 carries mitogen receptors with higher affinity and is enriched in two enzymes, (K+ + Na+)‐ATPase and acyl‐CoA:lysolecithin acyltransferase (Resch, K. et al., Biochim. Biophys. Acta 1978. 511: 176). Microsomal membranes, derived more than 85% from the plasma membrane, of mitogen‐activated calf thymocytes were fractionated by affinity chromatography into similar fractions like resting lymphocytes, i.e. into MF‐1 and MF‐2. The activities of various membrane‐bound enzymes and fatty acid incorporation into these subfractions were compared to the corresponding similar subf ractions of nonactivated thymocytes. It appeared that two enzymes which were involved in lymphocyte activation, i.e. (K+ + Na+)‐ATPase and acyl‐CoA:lysolecithin acyltransferase, were enriched in the adherent fraction MF‐2 of microsomes from both normal and mitogen‐activated thymocytes and that both were activated primarily in this fraction. Adenylate cyclase was moderately enriched in the MF‐2, but was marginally activated in both fractions of membranes of mitogen‐activated cells. Alkaline p‐nitrophenyl phosphatase, Mg2+‐ATPase and γ‐glutamyltransferase were more or less evenly distributed in the plasma membrane and were strongly inhibited in both fractions of membranes from mitogen‐activated cells. Although acyl‐CoA:lysolecithin acyltransferase was activated preferentially in MF‐2, it was found that isotopically labeled fatty acids incorporated into the phospholipid lecithin quickly diffused throughout the whole membrane. These results suggest that specialized areas of the plasma membrane exist around the high‐affinity mitogen receptors which initially respond to the binding of mitogens.
Human T lymphocyte receptors for IgM: control by IgG‐binding lymphocytes
Authors: Samarnt Christiane , Revillard Jean‐Pierre
Published: February 2007

The capacity of human peripheral blood lymphocytes to bind antigen‐IgG or antigen‐IgM‐antibody complexes was investigated using a rosette technique with ox erythrocytes (E) coated with rabbit IgG (AG) or IgM (AM) antibodies. EAM rosette formation was achieved only in suspensions pre‐incubated for 24 h at 37°C. Addition of either EAM or EAG complexes to the culture medium was shown to prevent the formation of EAM rosettes. The inhibition was reversible, it was not due to trace IgM contaminants in the IgG antibody fraction. It was not observed when lymphocytes depleted of EAG‐rosetting cells were incubated with EAG complexes. Inhibition of the expression of lymphocyte receptors for IgM can be regarded as a consequence of the modulation of surface receptors for IgG and involves an interaction between the two lymphocyte subsets bearing surface receptors for IgG and IgM, respectively. However, these experiments do not exclude the possibility that a few cells which bind EAG may lose their receptors by modulation and then express a receptor for IgM.
Idiotypic cross‐reactivity of human and murine phosphorylcholine‐binding immunoglobulins
Authors: Riesen Walter F.
Published: February 2007

The idiotypic cross‐reactivity of mouse and human monoclonal immunoglobulins with binding activity for phosphorylcholine (PC) was investigated, using an idiotypic antibody elicited against the PC‐binding human IgMFR. The isolated FR heavy chain proved to be a better inhibitor for the reaction of IgMFR with anti‐FR than the FR light chain, but the intact protein was necessary for full idiotypic expression. PC was an inhibitor only at concentrations greater than 10−3 M indicating that the idiotypic antibody was not combining site‐directed. Among the murine PC‐binding IgA myeloma proteins, MOPC 167 was found to be the best inhibitor, but its inhibitory capacity was about 4 orders of magnitude lower than that of the homologous IgMFR. McPC 603 was an even weaker inhibitor, while TEPC 15 effected no better inhibition than human monoclonal immunoglobulins without PC‐binding activity. MOPC 167 has a most similar binding specificity to IgMFR as indicated by the high affinity for choline of these two proteins. TEPC 15 and McPC 603, on the other hand, exhibit a much lower affinity for choline. In addition to their similarity in specificity, proteins FR and MOPC 167 show important structural similarities within parts of their heavy and light chain variable domains. The data provide some evidence for the existence of idiotypic cross‐reactivity between the two species man and mouse.
Initiation of the blastogenic response of lymphocytes by hyperoptimal concentrations of concanavalin A
Authors: Steen Harald B. , Lindmo Tore
Published: February 2007

The blastogenic response of human lymphocytes in vitro to hyperoptimal concentrations of concanavalin A (Con A) has been studied by means of volume spectroscopy (measuring cellular and nuclear volume), flow cytofluorometry (measuring cellular DNA content) and incorporation of [3H]thymidine ([3H]dThd). The optimal Con A dose with respect to [3H]dThd incorporation was about 30 u, g/ml. In cultures given hyperoptimal doses, e.g. 100 μg/ml, [3H]dThd incorporation was strongly inhibited, whereas the number of cells entering S‐phase and significantly increasing their cellular and nuclear volume was considerably larger than with 30 μg/ml. With 200 μg/ml Con A, which induced negligible [3H]dThd incorporation, the percentage of responding cells was even larger. Hence, doses of Con A, which were hyperoptimal with regard to [3H]dThd incorporation, induced blastogenic response, including DNA synthesis, in a larger percentage of the cells than did the optimal dose. However, in cultures with hyperoptimal Con A doses, the progression of the cell cycle stagnated mainly during S‐ and G2‐phase and few cells completed mitosis. Thus, the blocking effect of hyperoptimal doses was not confined to any particular point of the cell cycle. The reduced [3H]dThd incorporation, seen with hyperoptimal doses, is attributed partly to a failure of this assay under such conditions.
Antigen‐specific helper T cells are essential for cytotoxic T cell responses to metabolically inactivated stimulator cells
Authors: Pilarski Linda M.
Published: February 2007

Primed spleen cells respond well to metabolically inactivated stimulator cells while normal spleen cells do not. This observation has been interpreted as showing that cytotoxic T cell precursors are different from unprimed precursors in their antigen recognition requirements for induction. A different model is proposed here which accounts for these observations as due to enhanced helper cell levels in primed populations. Experiments are described in this study which test several predictions of this model. These experiments show that in the presence of in vitro primed helper T cells, normal cells are able to respond efficiently to glutaraldehyde‐fixed stimulator cells. The helper effect is antigen‐specific. Since unprimed spleen cells can be efficiently induced by metabolically active stimulators (γ‐irradiated cells) and can respond to glutaraldehyde‐fixed antigen (metabolically inactive cells) only in the presence of specific helper cells, it seems reasonable to propose that helper cell signals are enhanced by a nonantigenic property of γ‐irradiated stimulator cells requiring metabolic activity. It is also clear that glutaraldehyde‐fixed cells are anti‐ genically intact as helper cells, primed to antigens on γ‐irradiated stimulator cells, efficiently and specifically help a response to fixed stimulators. Conversely, helper cells primed in vitro to glutaraldehyde‐fixed stimulators recognize antigen on γ‐irradiated stimulator cells. The level of help generated in response to glutaraldehyde‐ fixed stimulator cells is at least 10‐fold higher in primed cells than in normal cells. In addition, primed spleen cells can be induced in vitro to yield helper function by both fixed or unfixed stimulator cells. Normal helper cell precursors are induced at least 100‐fold more efficiently by γ‐irradiated as compared to glutaraldehyde‐fixed stimulator cells. This work supports the idea that a major effect of priming, which allows primed cells to respond to metabolically inactive stimulators, is to enhance levels of helper T cells in the primed population.
Occurrence of β2‐microglobulin in mammalian lymphocytes and erythrocytes
Authors: Björck Lars , Åkerström Bo , Berggård Ingemar
Published: February 2007

Cell‐associated β2‐microglobulin (β2m) has been studied by quantitative techniques in lymphocytes and erythrocytes of guinea pig, rabbit, rat and man. β2m was solubilized by sonication followed by treatment with acid, deoxycholate or thiocyanate, and then determined by radioimmunoassay. The average number of β2m molecules per lymphocyte, estimated after acidification, varied between 0.89 × 105 and 7.1 × 105. Rat erythrocytes contained 3.0 × 103 molecules per cell, whereas no β2m was detected in red blood cells from the three other species. A relatively large part of β2m in the mammalian lymphocytes and in rat erythrocytes was present on the cell surface according to a radioimmunoassay procedure using anti‐β2m antisera that had been absorbed with the blood cells analyzed.
Ontogeny of cells involved in the suppressor circuit of the immune response
Authors: Ptak Wlodzimierz , Naidorf Kenneth F. , Strzyzewska Jolanta , Gershon Richard K.
Published: February 2007

Some macrophage (MΦ) cell surface structures which bind T cell‐derived factors remain intact after the MΦ are killed by heating at 56°C(but not 72°C) for 45 min. As a result, appropriately killed MΦ (HK MΦ) can act as competitive antagonists for those MΦ functions which are involved in binding and active presentation of T cell derived regulatory signals. By blocking the transmission of these signals with HK MΦ, we have found that the spleens of newborn mice contain considerable numbers of “latent” helper cells whose activity is not ordinarily seen because it is overridden by suppressor mechanisms. Similarities between these neonatal helper cells and a subset of adult T helper “inducer” cells (cell surface phenotype Ly‐1+; Ly‐2−,3−; IJ+; Qa l+), whose activity appears in significant numbers only after immunization, are described.
Serological analysis of antigen‐specific helper factors specific for poly‐L(Tyr, Glu)‐poly‐DLAla–poly‐LLys [(T, G)‐A–L] and LGlu60‐LAla30‐LTyr10 (GAT)
Authors: Howie Sarah , Parish Chris R. , David Chella S. , McKenzie Ian F. C. , Maurer Paul H. , Feldmann Marc
Published: February 2007

In vitro prepared antigen‐specific helper factors reactive to the synthetic polypeptide antigens poly‐L(Tyr, Glu)‐poly‐DLAla‐ ‐poly‐LLys [(T, G)‐A‐ ‐L] or LGlu60‐La30‐ LTyr10 (GAT) and bearing Ia determinants were analyzed serologically to determine the nature of the Ia determinants they expressed.

I subregion‐specific mouse anti‐Ia antisera were used, and showed that (T, G)‐A–L specific helper factor (HF) contains I‐A subregion‐controlled determinants, whereas GAT‐specific HF carries I‐J subregion‐controlled antigens. This unexpected finding was confirmed in both the H‐2k and H‐2b haplotypes, using a variety of anti‐I‐J antisera.

Rabbit anti‐Ia antisera also reacted with both HF which raised the possibility that the Ia determinants on HF may be carbohydrate in nature. The fact that HF has a low molecular weight and yet contains Ia determinants, antigen‐binding capacity and idiotypic markers is compatible with this interpretation.
Biphasic rate of synthesis of glycoconjugates, phospholipids and DNA in concanavalin A‐stimulated mouse thymocytes. Involvement of cortisone‐sensitive and ‐resistant subpopulations
Authors: van Eijk Ronald V. W. , Mühlradt Peter F.
Published: February 2007

The time course of the rate of labeling of membrane components (phospholipids, glycolipids and glycoproteins) and DNA was followed in concanavalin A‐stimulated CBA/J mouse thymocyte cultures. Two peaks of stimulated biosynthetic activity were noted, the first at the beginning of the cultivation and the second about 25 h later. Both early and late peaks of biosynthesis of membrane components were accompanied by blast transformation and were unimpeded by suppression of DNA synthesis by hydroxyurea.

Cortisone‐sensitive and cortisone‐resistant thymocytes were prepared by selective agglutination of the cortisone‐sensitive cells with peanut agglutinin (Reisner et al. Cell. Immunol. 1976. 25: 129) or cortisone treatment of the animals. Cortisone‐sensitive cells responded early, while the cortisone‐resistant population gave only the late response.

The autoradiographic patterns from sodium dodeeyl sulfate polyacrylamide gels of [3H]fucose or [3H]galactose‐labeled glycoproteins from early and late labeling cells, and cortisone‐resistant cells, were compared. Late‐labeling and cortisone‐resistant cells gave indistinguishable patterns, but differed significantly in their patterns from early‐labeling cells.

It is concluded that the two peaks of biosynthetic activity during the course of concanavalin A stimulation of thymocytes are caused by two different cell populations which require different times for maximal response and react independently of one another.
Mutations affecting immunoglobulin light chain secretion by myeloma cells I. Functional analysis by cell fusion
Authors: Mosmann Timothy R. , Baumal Reuben , Williamson Alan R.
Published: February 2007

Two clones of MOPC 315 cells have been selected which synthesize but do not secrete Ig lambda light chains. These clones were analyzed by fusion with a cell line synthesizing and secreting kappa chains. Conditions were established for recovery at high frequency (approximately 10−3) of spontaneously fused, viable hybrid cells. The resulting hybrid cell lines synthesized both kappa and lambda chains but secreted only kappa chains. Hybrid cells produced by fusion of a lambda‐secreting clone of MOPC 315 with the kappa‐secreting cell line were also isolated and shown to synthesize and secrete both kappa and lambda chains. These results suggest that the nonsecretion of lambda chains was not due to a defect in the secretion mechanism of the variant cells. A more likely alternative is that the lambda chains in the variant cell lines were structurally altered to a form which could not be secreted.
Inhibition of killer‐target cell interaction by monoclonal anti‐H‐2 antibodies
Authors: Lindahl Kirsten Fischer , Lemke Hilmar
Published: February 2007

The sites on target cells with which cytotoxic T lymphocytes interact were characterized using three different monoclonal BALB/c anti‐CBA antibodies derived from plasma cell hybrids. The antibodies all reacted with H‐2Kk and appeared to recognize public specificities H‐2.5,11 and 25, respectively. Allogeneic killing directed at products of H‐2Kk was inhibited by all three antibodies, irrespective of the H‐2 haplotype of the responder; cytotoxicity directed at products of another allele, H‐2Kd, or of the H‐2 D region on the same target cell was not affected. The antibodies did not inhibit killer cells carrying H‐2Kk. Cytotoxic reactions against minor histocompatibility antigens, including the male‐specific antigen H‐Y, were also blocked by all three monoclonal antibodies when restricted by H‐2Kk, but not when restricted by H‐2D on the same target cell. Cytotoxic T lymphocytes thus appear to interact with their target via the same, serologically defined H‐2Kk molecule which carries public specificities, whether they recognize it as an alloantigen or as self. This argues against the existence of separate H‐2 K‐encoded molecules recognized by killer cells only and against H‐2 specific modifications of minor histocompatibility antigens as the basis of H‐2 restriction.

One of the antibodies, 27 R9, which reacted with H‐2Kk and H‐2′ and was thought to recognize specificity H‐2.25, showed a weak cytotoxic reaction but bound with a high titer to H‐2 Dk, a reaction that has not previously been described. This antibody selectively and with a very high titer inhibited male‐specific cytotoxicity restricted by H‐2Dk, but did not significantly interfere with allogeneic killing against products of the H‐2 Dk region nor apparently with H‐2Dk‐ restricted cytotoxicity specific for other minor antigens. The results suggest the existence of at least two different restriction elements controlled by the H‐2Dk region.
The specificity of nonspecific concanavalin A‐induced helper factors
Authors: Bemabé Rosa R. , Martinez‐Alonso Carlos , Coutinho Antonio
Published: February 2007

Addition of supernatants from concanavalin A (Con A)‐stimulated spleen cells enable nude spleen cells to respond in vitro to a variety of antigens (in our experiments, sheep (SRBC) and horse erythrocytes (HRBC)). Experiments presented here, indicate that such nonspecific helper supernatants are in fact a polyclonal mixture of diverse, specif‐ ic activities. Con A stimulation of thoracic duct lymphocytes, specifically depleted of SRBC or HRBC‐reactive cells by the Sprent technique, results in a specific decrease in the activity to the relevant antigen. On the one hand, Con A stimulation of in vivo activated thymocytes results in the production of helper supernatants which are almost totally specific for the antigen used in priming.

In spite of these indications of specificity, it has been impossible to absorb out helper activity from normal Con A supernatants on the corresponding antigen. Specific removal of helper activity, however, can readily be achieved by absorbing helper supernatants on complexes of antigen and early immune sera. Various control ex‐ periments demonstrate that the loss of activity in the absorbed supernatants is not due to carry‐over of antibody into the test cultures. Furthermore, the fraction of helper activity that can be specifically removed on antigen‐antibody complexes depends on the conditions used in the preparation of the supernatants; this fraction is highest when Con A activation of T cells is performed in the presence of B cells without antigen.

These results suggest that “nonspecific helper factors” are a mixture of diverse molecules, some of which show specificity for variable regions of antibodies.
In vitro evidence from anti‐hapten antibody responses for T helper and suppressor cells directed against major histocompatibility antigens in the mouse. Participation of I region determinants in the induction of T helper cells
Authors: Vogt Peter , Simpson Elizabeth
Published: February 2007

The antibody response to murine alloantigens is thought to be thymus‐dependent. In this study, we were using H‐2 and H‐minor antigens presented on the surface of cells as particulate carriers and 2, 4, 6‐trinitrophenyl (TNP) as a hapten.

To study conditions for the induction of T helper and T suppressor cells directed against such antigens, T cell donor mice of a given inbred strain were primed with spleen cells of another inbred strain differing in distinct subregions of its H‐2 haplotype and/or differing in its H‐minor haplotype. Spleen T cells of mice in vivo allogeneically (carrier)‐primed in this way were cocultured in vitro with splenic in vivo TNP (hapten)‐primed B cells plus irradiated TNP‐conjugated spleen cells (hapten‐carrier conjugate) from the haplotype used for carrier priming.

The anti‐hapten antibody response was taken as a quantitative indicator of helper activity. Suppression was tested by measuring the reduction of the antibody‐forming cell response of in vivo TNP or sheep red blood cell (SRBC)‐primed B cells restimulated in vitro with homologous antigen in the presence of allogeneically primed T cells.

Helper cell functions were clearly demonstrated when donors of T cells were primed to Ia antigens. Additional priming to K and/or D antigens yielded help and suppres‐ sion simultaneously, priming to K and/or D antigens alone and in some cases to H‐ minor antigens yielded no help but resulted in strong suppression. The effect of the helper cells was shown to be camer‐specific occurring only in the presence of the relevant carrier, whereas the suppressor T cells were of the nonspecific type sup‐ pressing both anti‐TNP and anti‐SRBC responses in the absence of any restimulating carrier. The helper effect was seen not only when the hapten was conjugated to the appropriate (allogeneic) cells but also when it was presented on an unrelated carrier (syngeneic cells) provided that the specific nonhaptenated carrier was present. ‐ Pos‐ sible recognition mechanisms are discussed.
Studies on T lymphocyte activation I. Requirements for the mitogen‐dependent production of T cell growth factors
Authors: Andersson Jan , Grönvik Kjell‐Olov , Larsson Eva‐Lotta , Coutinho Antonio
Published: February 2007

Conditioned media (CM) obtained from concanavalin A (Con A)‐stimulated spleen cell cultures maintain mitogen‐derived T cell blasts in exponential growth for indefinite periods of time. Such purified T cell blasts do not respond to Con A, and the growth‐promoting activity in CM is independent of the mitogenic lectin used for its production. However, the appearance of activity in CM is Con A dose‐dependent. Furthermore, the production of these T cell growth factors is independent of B cells, while it requires both T cells and nontheta‐bearing, probably la‐positive cells present in normal and nude spleens. On the other hand, the T cell blasts which are reactive to the growth factors, neither produce CM by themselves nor can they cooperate with nude spleen cells for its production, in the presence of a mitogenic lectin.

Since the concentration of growth factors in CM determines the extent of T cell growth, we propose that the growth of some T cells is necessarily dependent upon the activity in CM described here and, consequently, that the basis for T cell activation is the induction of such growth factors.
Fine specificity of a continuously growing killer cell clone specific for H‐Y antigen
Authors: von Boehmer Harald , Hengartner Hans , Nabholz Markus , Lernhardt Waldemar , Schreier Max H. , Haas Werner
Published: February 2007

H‐Y‐specific cytotoxic T cells were first cloned in soft agar and grown over a period of 8 months in media conditioned with supernatants from mouse and rat spleen cells stimulated with concanavalin A. The specificity of cloned cells and their cytolytic potential remained essentially unchanged over the entire culture period. In addition to lysing male target cells expressing H‐2 Db antigens, the cytolytic cells lysed also male as well as female cells expressing H‐2 Dd alloantigens. Seventeen out of eighteen subclones derived from the original clone revealed the same activity. The cells divide about every 17–20 h and can be obtained in large quantities.
Significance of serum factors in the stimulation of human umbilical cord and fetal lymphocytes by soluble protein A from Staphylococcus aureus
Authors: Turunen Olli
Published: February 2007

Human umbilical cord and fetal lymphocytes were cultured in the presence of various sera [AB serum, fetal calf serum (FCS) and gammaglobulin‐free FCS] and soluble protein A from Staphylococcus aureus (SpA). Dose response studies showed that SpA in a final concentration of 100 μg/ml stimulated moderately cord blood lymphocytes. SpA‐induced DNA synthesis was significantly higher when cord lymphocytes were cultured with FCS than with AB serum or gammaglobulin‐free FCS. After 6 days' culture, even SpA without serum became a potent mitogen for these cells. The peak values for incorporation of thymidine into cord lymphocytes depended on the concentration of SpA and the serum used for culture. However, fetal splenocytes, thymocytes and peripheral lymphocytes reacted more avidly with SpA in cultures containing AB serum than FCS. Furthermore, serum‐free SpA cultures did not result in any activation of fetal lymphocytes. Regardless of whether cord blood lymphocytes were cultured with AB serum or FCS, both T and B subpopulations were stimulated. In contrast to fetal cells, the response of cord cells was stronger with FCS, and the peak values were shifted to later culture days.

In conclusion, SpA acts as a mitogen both on T and B cells in early fetuses as well as in the newborn. Serum factors significantly influence the strength and kinetics of the mitogenic response.
Helper activity of T cells stimulated in long‐term culture
Authors: Julius Michael H. , Augustin Andrei A.
Published: February 2007

Thymus‐derived (T) cells obtained from three categories of in vitro antigen‐induced proliferative responses were assayed as sources of helper T cells. These categories are exemplified by (a) direct stimulation of keyhole limpet hemocyanin (KLH)‐primed cells with KLH, which results in high indexes of proliferation; (b) direct stimulation of apoferritin‐primed cells with apoferritin, which does not result in indexes of proliferation above background levels; (c) trans‐stimulation of unprimed cells with X‐irradiated KLH‐primed cells which results in indexes of proliferation comparable to category (a).

Our results indicate that levels of [3H]thymidine incorporation by proliferating populations are not an accurate reflection of helper T cell generation. Directly stimulated KLH and apoferritin‐primed cells give rise to highly enriched populations of antigen‐specific helper T cells which support both IgM and IgG antibody responses in vitro. Moreover, these specific helper T cells are functionally restricted by products encoded by the I region of the major histocompatibility complex (MHC). Helper T cells generated in KLH‐trans‐stimulated cultures are not KLH‐specific in that comparable levels of helper activity are expressed using either KLH or apoferritin as carriers. These non‐KLH‐specific helper T cells only support the production of IgM antibody in vitro and they are not functionally restricted by MHC products.
Amino acid sequence analysis of group e allotype‐ related peptides derived from lagomorph IgG
Authors: Teherani Jane , Capra J. Donald , Aggarwal Shanti , Mandy William J.
Published: February 2007

A tryptic peptide (T19) was isolated from a CNBr fragment of IgG from several representatives of present‐day lagomorphs including domestic rabbit, hare, cottontail rabbit and pika. The amino acid sequence of this peptide revealed differences which can be correlated with serological polymorphism associated with group e IgG allo‐ types. The results confirm previous studies establishing the importance of Ala309 for the expression of e 15, particularly the i subspecificity. Arg315 correlates with the expression of the j subspecificity.
Regulation of the specific plaque‐forming cell responsein man: Restraint of B cell responsiveness
Authors: Dosch Hans‐Michael , Shore Abraham , Gelfand Erwin W.
Published: February 2007

Specific in vitro plaque‐forming cell (PFC) responses of normal human lymphocytesare antigen dose‐dependent, with bell‐shaped dose response patterns. Both the bell‐shaped antigen dose response characteristics as well as optimal PFC responseamplitudes are dictated by two distinct and separable T lymphocyte subpopulationswhich act on a nonlimiting set of PFC precursor B cells. Specific theophylline‐sensitive suppressor and theophylline‐resistant helper T cells are activated by antigen in adose‐dependent fashion. The initially small suppressor cell pool expands exponentially following antigen contact, whereas the larger helper cell population does not. This leaves a restricted range of antigen concentrations where net helper activity issufficient to promote a PFC response. Due to coinduced suppressor activity, PFCresponses showed an overall negative restraint at all antigen concentrations. Limitingdilution analysis suggested that it is the numerical balance between the two alternative T cell subsets which determines the extent of this negative restraint. These datadelineate a cellular mechanism for the translation of an antigenic stimulus into a B cellantibody response; theophylline‐sensitive suppressor cells are able to expand inresponse to this stimulus and represent the main regulative vector. Thus, in mixedlymphocyte populations, antigen concentration is a valuable probe for studies of thebalance of discrete T cell subpopulations but not for absolute B cell responsiveness.
Induction and characterization of delayed‐type hypersensitivity to influenza virus in mice
Authors: Liew Foo Y. , Russell Stuart M. , Brand Colin M.
Published: February 2007

Mice infected with an aerosol of influenza virus or immunized with purified UV‐ inactivated whole virus or viral subunits developed delayed‐type hypersensitivity (DTH) to influenza virus. The level of DTH was greatly enhanced when mice were injected intraperitoneally 2 days prior to immunization with 200 mg/kg of cyclophosphamide. The reaction peaked at 24 h after elicitation, had the classical DTH histology, and was transferable by immune cells but not by immune serum. DTH induced in cyclophosphamide‐pretreated mice persisted for at least 40 days after sensitization. DTH induced by deoxycholate‐treated subviral particles (DC particles) or the matrix protein of the influenza virus was type‐specific, i.e. DTH induced by DC particles or matrix protein of type A virus cross‐reacted only with type A virus and not with type B virus. DTH induced by purified hemagglutinin (HA) subunits, on the other hand, showed subtype specificty. Thus, DTH induced by HA of X 31 virus (H3) did not cross‐react with PR 8 virus (H 0). However, DTH induced by HA of one subtype cross‐reacted significantly with the variants of the same subtype. Thus, it appears that the effector T cells of DTH do not discriminate between the antigenic variants of influenza virus that are distinguishable by serology. DTH induced by purified, UV‐ inactivated whole virus showed extensive cross‐reactivity. This nonspecific reaction was shown to be due to host‐derived material, the lipid bilayer. ‐ The theoretical and practical implications of these findings are discussed.
Neonatal expression of a cross‐reactive idiotype associated with anti‐phenylarsonate antibodies in strain A mice
Authors: Nutt Nan B. , Wiesel Andrea N. , Nisonoff Alfred
Published: February 2007

Data are presented which indicate that B cells expressing the cross‐reactive idiotype associated with anti‐p‐azophenylarsonate antibodies of A/J or allotype‐congenic C.AL‐20 mice are present in neonatal mice. Data were obtained by direct immunization of neonatal mice or by adoptive transfer of cells from neonatal C.AL‐20 mice into idiotype‐negative BALB/c recipients. These findings, together with those previously reported for antibodies to phosphocholine in BALB/c mice, support the generalization that major cross‐reactive idiotypes may usually be found early in the life‐span of a mouse. The contrast between the frequency of appearance of the major cross‐reactive idiotypes and “private” idiotypes with the same antigen‐binding specificity, which are found after immunological suppression of the major idiotype, is consistent with the possibility that cross‐reactive idiotypes are the product of germ line genes or minor somatic variants of germ line genes while private idiotypes arise through somatic diversification. Alternatively, regulatory mechanisms may account for the striking difference. The present results are therefore consistent with the early expression of germ line genes controlling the major idiotype or of corresponding regulatory genes. The average concentration of idiotype, per unit weight of anti‐phenylarsonate antibody, is somewhat lower in neonatal than in adult A/J mice indicating that the major idiotype does not account for all of the antibody produced in response to this hapten in the neonate.
Ontogeny of immunity in amphibians: Changes in antibody repertoires and appearance of adult major histocompatibility antigens in Xenopus
Authors: Du Pasquier Louis , Blomberg Bonnie , Bernard Claude C. A.
Published: February 2007

Larval Xenopus anti‐2, 4‐dinitrophenyl antibodies of the low‐molecular weight type can be analyzed by isoelectric focusing (IEF). Within a clone of genetically identical animals, tadpoles make antibodies whose IEF spectrotypes are shared by most of the individuals. Adults of the same clone also make antibodies of identical spectrotype, but the adult pattern can be very different from the larval one, although both responses are heterogeneous. The larval spectrotypes that one cannot see in a primary adult response can be found if the adult has been primed during larval life and boosted after metamorphosis. The heterogeneity of the response is somewhat lower in tadpoles (up to 12 antibody IEF bands) than in adults (up to 20 antibody IEF bands). The change in the repertoire occurs during metamorphosis at the time of the appearance of two major histocompatibility complex antigens. One, a lymphocyte antigen, appears 10‐15 days before the end of metamorphosis, the other, present on red cells (and presumably also on lymphocytes), appears 1.5 month after the end of metamorphosis, as determined by immunofluorescence analysis. During the same period, the syngeneic mixed leukocyte reaction switches from a larval anti‐adult to an adult anti‐larval reaction.
Characteristics of the T‐dependent α(1 → 6) glucosyl (dextran) antibody response induced in mice with isomaltohexaose coupled to chicken γ‐globulin
Authors: Moreno Carlos , Hale Christine , Hewett Rosemary , Cussell Deborah
Published: February 2007

Isomaltohexaose flavazole coupled to chicken γ‐globulin (IM6‐CGG) induced T celldependent anti‐α( 1 → 6) dextran‐specific IgM and IgG responses in CBA, BALB/c and A strain mice. The IgG responses were of restricted heterogeneity as judged by isoelectric focusing, and belonged mostly to the IgG1 subclass with a minor IgG3 component in the case of BALB/c and CBA mice. All four subclasses of IgG were produced in A strain mice. In contrast, native dextran B 512 induces exclusively T cell‐independent IgM responses of the same specificity for all 3 strains.

All BALB/c mice immunized with different doses of IM6‐CGG either in Freund's adjuvant or with A1(OH)3 plus Bordetella pertussis showed the same spectrotypes by isoelectric focusing. Sera obtained at different times after immunization of BALB/c mice failed to show spectrotype variations. Late, but not early, bleedings from CBA mice showed a tendency towards more uniform isoelectric focusing patterns.
A mature T lymphocyte subpopulation marker closely linked to the Ig‐1 allotype CH locus
Authors: Owen Frances L. , Finnegan Alison , Gates Edward R. , Gottlieb Paul D.
Published: February 2007

An antiserum raised in BALB/c AnN mice against selected CAL.20 T cells reacts with a cell surface antigen in virgin animals that is found on 25% of mature thymocytes and Lyt‐2‐bearing T cells, but not on prothymocytes, Lyt‐1 T cells or B cells. The antigen is restricted to strains carrying the Ig‐ld or Ig‐le heavy chain allotype haplotypes. It is expressed in F1 mice. The antiserum blocks the binding of suppressor T cells to the cross‐reacting idiotype for arsonate while reagents specific for Fab, Fc or Ig were ineffective. We suggest that the antigen described represents a determinant on the product of a new locus coding for a heavy chain‐linked polypeptide found on a subpopulation of T cells.
Partial N‐terminal amino acid sequence analyses and comparative tryptic peptide maps of murine Ia molecules encoded by the I‐A subregion
Authors: Cecka J. Michael , Millan Minnie Mc , Murphy Donal B. , McDevitt Hugh O. , Hood Leroy
Published: February 2007

The partial N‐terminal amino acid sequences and tryptic peptide maps of I‐A subregion products from the H‐2b, H‐2d, H‐2k and H‐2S haplotypes demonstrate that haplotype‐associated differences are present in both a and β polypeptides. The genetic and evolutionary implications of these multiple amino acid substitutions and the homology relationships among Ia molecules from human, guinea pig and the I‐E subregion of the mouse are discussed.
Radioimmunoassay determinations of murine β2‐microglobulin and an H‐2 antigen‐like serum component
Authors: Kvist Sune , Peterson Per A.
Published: February 2007

Normal mouse serum contains H‐2 antigen‐like components. One such protein consists of a 40000 dalton chain and β2‐microglobulin (β2m) and the other component contains the two H‐2 antigen‐like subunits and, in addition, two larger polypeptide chains with apparent molecular weights (mol. wt.) of 65000 and 80000. Radioimmunoassay procedures specific for the H‐2 antigen‐like chain and β2m, respectively, have been developed. Whereas free β2m and β2m associated with other polypeptide chains reacted identically in the β2m radioimmunoassay, the two serum forms of the H‐2 antigen‐like chain displayed different reactivities in the heavy‐chain assay. The low mol. wt. protein complex, comprising the 40000 dalton chain and β2m, inhibited in the heavy‐chain assay identically with the standard. However, the high mol. wt. complex containing the H‐2 antigen‐like chain gave rise to a biphasic inhibition profile. This was apparently due to some antigenic determinants of the 40000 dalton chain being buried by the 65000 and 80000 dalton chains. Inhibition curves parallel with the standard were, however, obtained on dissociation of the high mol. wt. protein complex with sodium dodecyl sulfate. Thus, by subjecting serum to the ionic detergent‐sensitive radioimmunoassay, procedures for the two H‐2 antigen‐like chains could be developed.

The serum levels of the H‐2 antigen‐like chain and of β2m vary with the age of the animal, and adult levels are recorded only at 6 to 7 weeks of age. The serum concentrations of the two proteins are strongly correlated. The H‐2 haplotype appears to partly regulate the serum levels of the two proteins. Mice of the H‐2f haplotype contain about 40‐fold lower levels of the H‐2 antigen‐like chain than do mice of other strains.
Surface Ig on rabbit lymphocytes Rabbit B and T cells are distinct populations
Authors: Bast Bert J. E. G. , Catty David , Manten‐Slingerland Ria , Jansen Jan T. G. , Veldhuis Dick H. , Roholl Paul , Ballieux Rudy E.
Published: February 2007

Rabbit peripheral blood lymphocytes (PBL) were analyzed by immunofluorescence using anti‐T cell conjugates and anti‐Fab, anti‐al allotype, anti‐IgM and anti‐IgA conjugates. In addition, T cells were demonstrated by rosetting with papain‐treated homologous erythrocytes. Control experiments, using acid treatment and incubation at 37 °C for 18 h after or without pronase treatment, revealed the endogenous origin of all surface determinants tested.

A good correlation was found between results obtained with the two anti‐T cell conjugates used and the T rosette test on PBL and on lymphoid cells isolated from various organs. In lymphocytes isolated from peripheral blood and from various lymphoid organs, the percentages of T and B cells were respectively 45 and 38 for PBL, 10 and 46 for bone marrow, 27 and 31 for appendix, 40 and 45 for spleen, 42 and 46 for Peyer's patches, 96 and 0.3 for thymus and 70 and 16 for peripheral lymph nodes. The percentage of “null” cells in lymphocyte populations derived from bone marrow and appendix is rather high. The final percentages of T and B cells in rabbit PBL depend to a significant extent on the method of isolation, especially isolation by Ficoll‐Hypaque centrifugation results in a depletion of T cells. Moreover, a rather impure lymphoid cell suspension is obtained.

In double incubation experiments, T cells (as defined by T cell antigen(s) or rosette formation) and B cells (Fab‐bearing cells) were entirely different subpopulations. Allotypes of the a locus could not be detected on the surface of T cells. The results are discussed with respect to genetic coding of antigen receptors on B and T cells.
Immunologically active zones in bovine growth hormone
Authors: Ferrara Pascual , Zakin Mario M. , Peña Clara , Paladini Alejandro C.
Published: February 2007

Antigenic determinant areas were detected in bovine growth hormone fragments 6–124 and 125–149, the former being predominant. Reduction and carboxymethylation of disulfide bridge 53–164 destroys the immunological reactivity of the area which is little affected by reduction and carbamoylmethylation. All the activity found in fragment 6–124 seems to be concentrated in the sequence 87–124.