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Biomedical subjects

M Seman

Publications and source records attributed to M Seman.

At least 73 records · Page 4Linked to original sources
PubMed1984

Immune response to the p-azobenzenearsonate-L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) conjugate. III. Mechanisms of Ir gene-controlled phenotype conversion.

Immunization of GT (random copolymer of L-glutamic acid51-L-tyrosine49) nonresponder animals with p-azobenzenearsonate (ABA) GT conjugates elicits an antibody response to both ABA and GT epitopes which is induced by ABA-specific T helper cells. Expression of these hapten-specific helpers is under the control of an I region gene which also regulates the proliferative T cell response to ABA. Conversion of the unresponsive phenotype to GT is, therefore, dependent on the ABA Ir gene and escapes the influence of the GT-specific I region-controlled suppressive pathway. Studies on the influence of ABA/polymer coupling ratio on T and B cell responses suggest that ABA-specific T cells, like conventional carrier-specific helpers, require linked interactions with B lymphocytes to provide helper signals. GAT (terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10) nonresponder animals immunized with ABA-GAT conjugates also develop an antibody response to ABA which is induced by ABA-specific T helper cells. Comparison of antibody affinity, specificity, isotypes and idiotypes in different mouse strains demonstrates that hapten-specific helper cells stimulate antibody responses to ABA which are qualitatively similar to those induced by GAT-specific helpers. However, ABA-specific helper cells do not permit the conversion of the I region gene-controlled nonresponder phenotype to GAT. The data suggests that high ABA density, which is required for optimal ABA help expression, extinguishes the immunogenicity of GAT determinants at both T and B cell levels.

Animals↗
PubMed1984

Helper functions of antigen-induced specific and autoreactive T cell colonies.

Helper T cells have been distinguished on the basis of whether they provide carrier-specific or nonspecific helper functions. In previous experiments we determined that the predominant class of helper T cell in populations of primed lymph node cells is a nonspecific helper T cell unable to provide carrier-specific signals. Initial induction of nonspecific helper T cells in vitro requires restimulation with the immunogen. This suggested that such T cells may express antigen-specific receptors. In this case they would constitute a unique subpopulation distinct from T cells with identical antigen-specificity that are able to provide carrier-specific help. Alternatively, the requirement for antigen restimulation might reflect a role for antigen-specific T cells in the recruitment of T cells with unrelated specificity. To distinguish between these possibilities we have characterized the specificity and function of helper T cell colonies selected from primed lymph node cells. We report here isolation of autoreactive as well as antigen-specific helper T cells. All antigen-specific T cell colonies provide carrier-specific help in the presence of the homologous hapten-carrier conjugate. Only autoreactive T cells are limited to providing nonspecific helper function. Although selection of autoreactive T cells is initially dependent on antigen restimulation in vitro, activation of an established autoreactive T cell line requires restimulation with MHC-syngeneic spleen cells but does not require restimulation with either the immunogen or fetal calf serum. These results suggest that nonspecific helper T cells induced in the course of a normal immune response to randomly chosen foreign antigens are autoreactive. Such T cells may serve to enhance proliferation and maturation to immunoglobulin secretion of B cells activated by limiting numbers of carrier-specific helper T cells. The demonstration of large numbers of precursors to MHC-specific autoreactive T cells in antigen-primed populations raises important issues concerning regulation of the expansion of autoreactive T cells in vivo.

Animals↗
PubMed1984

Interaction between genes of chromosome 12 and I-region genes in the control of the arsonate-specific T cell repertoire.

The T lymphocyte repertoire consists of clones recognizing foreign antigens together with self histocompatibility molecules. Diversification of the receptor is believed to arise by somatic mechanisms during ontogeny. MHC gene products are essential for this process as well as for antigen recognition and expression of T cell functions. Yet, the antigen-specific T cell receptor is not encoded by MHC genes. Little is still known concerning the nature and the genetic origin of this receptor despite numerous experimental approaches. Although the T cell repertoire is mainly determined, in a single individual, by the alleles expressed at the MHC locus, one can postulate that it could also be influenced by the existence of alleles of the germ line gene(s) encoding the T cell receptor. If so, an analysis of the T cell fine specificity in mice of the same H-2 haplotype with different background genes might permit the mapping of the genes coding for this receptor. Such an experimental approach requires the use of an antigen consisting of only one major determinant. Several recent observations suggested to us that the hapten p-azobenzenearsonate (ABA) was a suitable model for such investigations. Thus, we decided to compare the specific pattern of responses to ABA-tyrosine, ABA-histidine and to free ABA in different inbred mouse strains. We report here that the lymph node T cell proliferative response to these molecules is under the control of an ABA-specific Ir gene. The ABA-Tyr conjugate is the most potent immunogen of the three in vivo as well as in vitro. High responder strains to ABA-His or ABA are included in the group of high responders to ABA-Tyr suggesting that the response to the three molecules is under the control of the same Ir-gene. The pattern of the response is also influenced by background gene(s). One of these can be localized on chromosome 12 using congenic mice. No close linkage to IgCH markers or VH idiotypes can be demonstrated but a linkage of this gene(s) to the Pre-1 locus seems possible. B lymphocytes do not seem to account for the involvement of Chr.12-genes in the response since; in our experimental system, they do not present ABA to T cells nor do they proliferate in the assays. Similarly, ABA-Tyr-antibody complexes do not enhance macrophages presentation of ABA to T cells, which supports the conclusion that IgCH or VH gene products are not involved in the control of the response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Immune response to the p-azobenzenearsonate (ABA)-GAT conjugate. II. Hapten-specific T cells induced with ABA-GAT in GAT responder X nonresponder F1 hybrids are restricted to the nonresponder haplotype.

Immunization of mice with the ABA-GAT conjugate stimulates GAT-specific T helper cells in GAT-responder animals and ABA-specific helpers in nonresponders. Unexpectedly, immunization of (responder X nonresponder) F1 mice, which have the GAT-responder phenotype, leads to the recruitment of both ABA- and GAT-specific clones of T helper lymphocytes. The GAT-reactive population is restricted to the haplotype of the responder parent (Iak), whereas ABA-specific T cells are mostly restricted to the nonresponder one (Ias). This is demonstrated by the ability of monoclonal antibodies to parental la antigens to inhibit T cell proliferation to GAT or ABA-Tyr in vitro. Consistently, ABA-GAT-primed F1 T cells can only activate nonresponder B cells to proliferate in the presence of ABA-Tyr and responder B lymphocytes in the presence of GAT. Furthermore, F1 T cells seem to recognize both ABA and GAT epitopes only in association with molecules encoded by the I-A subregion. Analysis of ABA-specific F1 T cell lines generated by in vitro stimulation with ABA-Tyr or ABA-GAT demonstrates a competition between GAT- and ABA-specific T cells present in the hybrid T cell repertoire and restricted to the same parental I-Ak molecule. The results indicate that F1 macrophages can present both ABA and GAT epitopes to T cells in association with the two parental and hybrid Ia determinants. It seems unlikely that the absence of GAT-specific T cells restricted to the nonresponder I-A in the F1 is due to suppressor T cells. Thus, the competition model that we propose, to explain the selective F1 T cell response to ABA-GAT, leads us to believe that GAT nonresponder animals may lack clones capable of recognizing, with a high affinity, I-As + GAT.

Animals↗
PubMed1983

Is the delayed-type hypersensitivity observed after a low dose of antigen mediated by helper T cells?

In mice receiving, i.v., a dose of antigen optimal for antibody response, no delayed-type hypersensitivity (DTH) reaction is detectable. In contrast, in mice receiving a dose of antigen too small to induce B cell activation, a DTH reaction is elicitable shortly and transiently after immunization. Using a sensitive titration assay of DTH-mediating T lymphocytes, this reciprocal relationship between antibody production and DTH responses was reinvestigated. The absence of peripheral DTH reactivity in mice primed i.v. with a high dose of antigen (10(9) heterologous red blood cells) does not result either from the absence of activation and clonal expansion of DTH-mediating cells or from induction of suppressive mechanisms but results from a decreased circulation of DTH-mediating cells. The present studies show that DTH-mediating cells disappear from blood to enter the spleen only when specific B lymphocytes are present and activated by a high dose of antigen. These results are compatible with the hypothesis that T cells activated by antigen can function either as helper cells for B lymphocytes or as DTH-mediating cells, depending on the environment they reach during their migration. In order to demonstrate that the same cell may support the two functions, monoclonal T lymphocytes were assayed for their helper function and for their ability to transfer a DTH reaction.

Animals↗
PubMed1982

Genetic control of sensitivity to moloney leukemia virus in mice. VI. Involvement of virus-specific T helper cells collaborating with B cells.

T cell responses to Moloney virus involve cytolytic and helper lymphocytes. In contrast to specific cytolytic T lymphocytes, few studies have been devoted to the characteristics of helper T cells for antibody production. The present experiments describe an assay for Moloney virus-specific help for B cells using dinitrophenylated virus. This method, using the Moloney virus as a carrier in a hapten-carrier system, allows to definition of the specific helper function of antibody responses. T helper cells were induced in murine sarcoma virus or inactivated Moloney murine leukemia virus-primed spleens or lymph nodes. T helper function was due to Thy-1.2, Lyt-1+2- cells and was macrophage-dependent. It was stimulated by whole virus of Moloney gp71 envelope protein but not Moloney p30 internal protein. Cross-reactive stimuli were obtained with other dinitrophenylated type C viruses. High and low responses were correlated respectively with resistance and susceptibility to Moloney leukemia virus. Cultures of helper T cells with preserved activity have been established and maintained for one month.

Animals↗
PubMed1982

Functional analysis of GAT-specific T cell clones: H-2-restricted monoclonal T helper cells do not regulate expression of antibody isotypes.

We obtained T cell clones specific for poly (Glu60, Ala30, Tyr10) (GAT) from GAT-primed lymph node cells of BALB/c mice. The clones consisted of helper cells that were carrier-specific and H-2-restricted and required a hapten-carrier bridge to activate B cells. They may be considered TH1 cells. They could all induce antibody responses of various isotypes in adoptive transfer in vitro. Isotypic patterns of the responses obtained with the clones were identical to those obtained with polyclonal T cells and were not dependent on the number of T helper cells added to the culture. Therefore, our observations demonstrate that classic TH1 cells do not regulate isotype expression on secondary responses. The expression of idiotype-like determinants on the GAT-specific clones was assayed. A syngeneic anti-idiotypic serum (B658), prepared in BALB/c mice against BALB/c anti-GAT antibodies previously characterized, was shown to block specifically the helper activity of GAT-specific T cell lines from BALB/c mice. Under the same experimental conditions the activity of none of the BALB/c clones was affected by serum B658.

Animals↗
PubMed1982

Immune response to the p-azobenzenearsonate (ABA)-GAT conjugate: role of I region genes in the selective activation of ABA-specific or GAT-specific T helper cells.

Immunization of GAT non-responders with ABA-GAT leads to the activation of ABA-specific T cells. These hapten specific T cells are Lyt-1+2- helper cells capable of inducing anti-ABA antibody responses in vivo or B cell activation in vitro. However, their activation does not modify the GAT non-responder phenotype. Immunization of GAT responder mice with ABA-GAT activates GAT-specific T cells, which can help anti-ABA and anti-GAT antibody responses. Since the responder and non-responder strains used in these experiments differ only in the alleles present in the I region, the results suggest that the selective activation of hapten- or carrier-specific T cells is controlled by I region genes. Yet sensitization of the two strains with ABA-KLH or ABA-Tyr induces KLH-specific or ABA-specific T cells, respectively. This provides further evidence that the use of an immunogenic carrier prevents the expression of the hapten-specific T cell clones present in the repertoire of both responder and non-responder animals. Macrophages from responder animals pulsed with ABA-GAT can present ABA and GAT determinants to T cells. Thus, the absence of ABA-specific T cells in responders primed with ABA-GAT and their presence in GAT non-responders reflects a competition between hapten- and carrier-specific T cells and not an epitope selection by macrophages. We discuss the significance of the results in terms of Ir genes determining the self-plus-antigen-specific T cell repertoire rather than controlling antigen presentation by macrophages.

Animals↗
PubMed1982

Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte.

In vivo primed T cells injected in the footpad of naive recipients elicit a typical delayed-type hypersensitivity (DTH) reaction in the presence of their specific antigen. The values of the footpad swelling obtained after these transfers show a clear distinction between negative and positive responses. Serial dilutions of primed T cell populations allow the establishment of titration curves by limiting dilution analysis according to Poisson distribution. The single hit titration curve indicates that a unique cell type underlies the DTH reaction. Furthermore, by using cloned T cells it can be demonstrated that the transfer of a single cell is able to initiate a DTH reaction. The revelation of T cell activity at unit level needs an optimal dose of antigen mixed with the sampled cells.

Animals↗
PubMed1981

Complementation between a gene of the I-E subregion and a non-H-2 gene in the class-specific suppression of IgG2a antibody to sheep erythrocytes.

A low level of IgG2a antibodies is observed in B10 mice after primary immunization with SRBC. Analysis of the response in different H-2b mice and among B10 animals with different H-2 haplotypes reveals that this selective isotype deficiency is under the control of at least two genes: a background gene and an H-2-linked gene. Responses of H-2 recombinant B10 strains map the H-2-linked gene to the 1-E subregion. Evidence is presented for complementation between H-2 and non-H-2 genes in the determination of the low responder phenotype. Low responsiveness appears to be inherited as a dominant trait. Possible functions of the two series of genes are discussed in relation to suppressor mechanisms.

Animals↗
PubMed1981

A delayed-type hypersensitivity reaction initiated by a single T lymphocyte.

In vivo primed T cells injected into the footpad of naïve recipients elicit a typical delayed-type hypersensitivity (DTH) reaction in the presence of their specific antigen. Serial dilutions of primed T cell populations were used in order to score positive and negative transfers. The values for the footpad swelling obtained after these transfers followed a bimodal distribution. This clear bimodal distribution with no overlapping between positive and negative transfers suggested that a single cell initiates the DTH reaction. Limiting dilutions of cloned T cells transferred with their antigen allowed us to demonstrate that a single cell is able to transfer a specific DTH reaction.

Animals↗
PubMed1979

Genetic control of the IgG2a response to sheep erythrocytes in mice: isotype- and antigen-specific T cell-mediated suppression in low responders.

The IgG2a response to sheep erythrocytes is examined in different congenic strains of mice. B10, B6, and C57BL/Ks animals produce a low level of IgG2a antibodies to SRBC during the primary response in vivo. They remain low responders after secondary challenge in vitro. Total spleen cells or nylon-purified T cells from these low responders inhibit the IgG2a response of H-2 compatible-responding mice in a mixed culture system. This suppression is mediated by Thy-1+, Ly-1-, Ly-2+, and I-J+T cells only present in the spleen of low responding animals. These suppressor T cells appear to be IgG2a- and SRBC-specific. Function of non-H-2-linked genes as regulators of suppressor T cells differentiation is discussed.

Animals↗
PubMed1978

Evidence for independent genetic regulation of the expression of different antibody classes in anti-sheep red blood cell responses.

Three levels of variation are described in the response to sheep red blood cells (SRBC). Inbred strains of mice are distinguishable in terms of early or late kinetics of IgM response, high or low overall IgG response, and the relative expression of IgG1, IgG2a and IgG2b antibody in their response to SRBC. Results using C57BL/10 hybrid progeny strongly suggest a genetic control of these different aspects of the anti-SRBC response. The IgM kinetic pattern and the quantitative IgG response are regulated by two independent multigenic systems. Evidence is also presented for a distinction between the genes controlling the quantitative IgG response and those which control the 7 S isotypic pattern. IgG2a antibody expression seems regulated by a single gene. Neither group of genes involved in these various types of regulation seems directly linked to the H-2 complex or to the CH allotype. The hypothesis that 4 different sets of genes might control IgM, IgG1, IgG2a and IgG2b expression is discussed.

Animals↗
PubMed1977

[Morphological diagnosis of Pneumocystis carinii].

Pneumocystis carinii pneumonia can only be diagnosed once the microorganism is demonstrated. The authors review and illustrate various staining technics, and discuss for each of them specific advantages. All samples must by systematically examined both by phase contrast microscopy and by light microscopy after Gomori-Grocott and Gram-Weigert stains. This morphological study is completed by ultrastructural photographs.

Humans↗
PubMedDate not supplied

Membrane effects of the polyene antibiotic amphotericin B and of some of its derivatives on lymphocytes.

Amphotericin B (AmB) exhibits immunomodulating properties in mice. In vitro studies on lymphocytes, in relation with these properties, are reported here with AmB and two of its derivatives: the N-Fructosyl (N-Fru AmB) and the N-thiopropionyl (AmBSH) derivatives. Interactions of these molecules with thymocytes, a sensitive cell type, demonstrated that the extent of binding is not a toxicity parameter. In contrast, membrane fluidity changes have been observed and appeared to be related to toxicity. Experiments performed with normal B lymphocytes have shown that Amphotericin B derivatives were more potent polyclonal B cell activators than the parent compound. To go further in the understanding of these events, we have investigated in a B cell line WEHI 231, the changes in intracellular Ca2+ and membrane potential induced by AmB and AmBSH. The two polyenes were shown to induce membrane depolarization but no intracellular Ca2+ increase.

Amphotericin B↗