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Biomedical subjects

M Feldmann

Publications and source records attributed to M Feldmann.

At least 397 records · Page 22Linked to original sources
PubMed1977

The role of macrophages in the generation of T helper cells. V. Evidence for differential activation of short-lived T1 and long-lived T2 lymphocytes by the macrophage factors GRF and NMF.

The generation of T helper cells in vitro requires macrophages or macrophage-derived factors such as genetically related macrophage factor (GRF) or nonspecific macrophage factor (NMF). However, there is a basic difference of T helper cell induction when using particulate antigens. The present study demonstrates that this difference is based on the activation of two different T cell subsets. GRF activates short-lived 'T1' cells which amplify the induction of T2 cells, which are the helper cell precursors. Thus, the genetic restriction of T helper cell induction seen with soluble antigen or GRF lies on the level of macrophage or GRF interaction with T1 cells. NMF (or macrophages) and particulate antigens directly activate the helper cell precursor (T2) indicating no requirement for T1-T2 cooperation. The direct activation of the helper cell precursor with particulate antigens does not require histocompatible macrophages or NMF from histocompatible macrophages. The present results may explain some of the discrepancies reported in the literature concerning the genetic requirements and specificity of T cell activation.

Animals↗
PubMed1977

Requirement for interactions between two subpopulations of T cells for helper cell induction in vitro.

The evidence for the interaction of 2 subpopulations of T cells, short-lived cells sensitive to adult thymectomy (T1 cells), and long-lived recirculating cells, sensitive to the action of antilymphocyte serum (T2 cells) in the induction of helper cells is presented. This T-T interaction occurred across a cell-impermeable nucleopore membrane, indicating that it did not depend on cell contact, but was mediated by subcellular factors. There was no genetic restriction on this T-T interaction, if it was performed across a nucleopore membrane. The implications of these results on our concepts of the mechanism of help are discussed.

Animals↗
PubMed1977

Expression of alloantigens LY-5 and LY-6 on cytotoxic effector cells.

With anti-Ly antisera and complement it has been possible to demonstrate that cytotoxic effector cells generated in vitro against allogeneic cells carry the alloantigen Ly-5 and Ly-6. The studies show that antisera directed against the Ly-6 antigens, together with complement, eliminate essentially all of the killer cells, of the appropriate strain, while killing only 50 to 60% of Thy-1+ cells. Anti-Ly-5 antsera and complement lysed 55 to 65% of Thy-1+ cells and killed a significant portion, but not all, of the cytotoxic cells. The later finding was investigated in more detail since it suggested a degree of heterogeneity within the killer cell subpopulation. However, the data did not support that conclusion, at least for allogeneic killer cells.

Animals↗
PubMed1977

In vitro studies on H-2 linked unresponsiveness. 1. Normal helper cells to (T,G)-A-L and GAT in low and non-responder mice.

Lymphoid cells from unprimed high responder (C57BL/10) and low responder mice (B10.Br, B10.A, CBA) to (T,G)-A-L and high responder (B10, B10.A) and non-responder (B10.G, DBA/I) mice to GAT can be induced to form antigen specific T-helper cells in vitro under identical culture conditions. The helper cells induced from high and low or non-responder mice appear to be identical in efficiency, antigen concentration requirement for induction and induction kinetics.

Animals↗
PubMed1976

Immunological effects of IgT synthesized by theta-positive cell lines.

The effects of immunoglobulin (Ig) purified by affinity chromatography from two cultured T cell lines on in vitro immune responses was studied. IgT purified from both EL-4 and WEHI-22 suppressed the thymus-dependent IgM response, but had no effect on the thymus-independent IgM response. In contrast, the IgG responses to both thymus-dependent and independent antigens were augmented at optimal concentrations of IgT. Ig of B cell origin--serum Ig, myeloma Ig, B cell surface Ig -- did not have any of these effects. Because of the similarity of the effects of IgT purified from the lymphomas with the effects of T cells and their IgT, it seems likely that the IgT obtained from EL-4 and WEHI-22 cell lines are analogues of normal IgT and thus should be useful in elucidating some of the chemical and biological properties of IgT.

Animals↗
PubMed1976

Suppressor cell induction in vitro. I. Kinetics of induction of antigen-specific suppressor cells.

The induction of antigen-specific suppressor cells in vitro, using high concentrations (100 mug/ml) of keyhole limpet hemocyanin (KLH) in Marbrook flasks is described. Spleen and cortisone-resistant thymocytes were the richest source of suppressor cell precursors, compared to lymph node cells, peripheral blood lymphocytes or thoracic duct lymphocytes. Suppressor cells induced with KLH only suppressed KLH-reactive helper cells, and not B cells or helper cells of other specificity. The suppressor cells were T cells, as judged by their sensitivity to anti-Thy-1.2, heterologous anti-T, but not anti-B antisera.

Animals↗
PubMed1976

Suppressor cell induction in vitro. II. Cellular requirements of suppressor cell induction.

The cellular requirements for the induction of antigen-specific suppressor cells (SC) in vitro were studied. Macrophage depletion, by either nylon wool or polystyrene columns or iron (and magnet) treatment or a combination of methods, did not diminish SC induction, in contrast to its effect on helper cell induction. The requirement for T-T interaction in SC induction using splenic T cells was studied by the use of adult thymectomy and anti-lymphocyte serum, which selectively deplete short-lived and recirculating T cells respectively. Since suppressor cell induction was markedly diminished, or abolished by either procedure, but reconstituted by mixing these 2 populations, it was concluded that there was T-T interaction in the development of SC, just as there is in the induction of other T cell reactions, such as the graft-versus-host response, the T killer cell response, the helper cell response and, tentatively, delayed hypersensitivity. By the use of double-chamber tissue culture flasks, with the 2 cell populations separated by a cell impermeable membrane, it was found that T-T interaction does not require cell contact and is thus mediated by factor(s). The direct precursor of antigen-specific suppressor cells is resistant to adult thymectomy but sensitive to anti-lymphocyte serum.

Animals↗
PubMed1976

Role of macrophages in the generation of T helper cells. IV. Nature of genetically related factor derived from macrophages incubated with soluble antigens.

Macrophages incubated with soluble antigens for 1-4 days release factors capable of inducing T helper cells. The nature and some of the properties of this genetically related macrophage factor (GRF) were investigated. By use of immunoadsorbents, GRF was shown to contain I region-coded products (Ia antigens) linked to a small antigenic fragment. The genes coding for the Ia antigens detectable in GRF lie in the I region of the H-2 complex. GRF does not react with anti-immunoglobulin, anti-C3 or anti-human beta2-microglobulin antisera, and its activity cannot be removed by antigen immunoadsorbents. GRF is heat-labile, sensitive to proteolytic enzymes and has a molecular weight of about 55 000 Daltons. The relationship of GRF to other factors known to contain I region-coded products and reported to be effective in cell cooperation is discussed.

Animals↗
PubMed1976

Role of epitope density in the induction of tolerance and immunity with thymus-independent antigens. III. Interaction of epitope density and receptor avidity.

The induction of B cell tolerance to 2,4-dinitrophenyl conjugates of polysaccharide antigens (levan or dextran) was studied in mice primed with keyhole limpet hemocyanin (KLH) or 2,4,6-trinitrophenylated KLH. The relationship of the epitope density of the tolerogen with avidity of B cell receptors (as judged indirectly by a plaque inhibition assay) was investigated. It was found that high avidity precursors (IgG) were tolerized by antigen of much lower epitope density, and at lower concentration, than were low avidity precursors (especially IgM cells). IgA cells were intermediate in behavior. These results suggest that the epitope density effect acts by ensuring a necessary degree and/or energy of antigen binding.

Animals↗
PubMed1976

Secondary cytotoxic allograft responses in vitro. III. The immunogenicity of allogeneic membrane fragments.

The immunogenicity of murine membrane fragments was tested both in primary and in secondary in vitro cytotoxic allograft responses, and compared to that of intact allogeneic stimulator cells. Allogeneic membrane fragments induced poor proliferative and cytotoxic responses in normal splenic responder cells. However reexposure of immune responder T cells to allogeneic membrane fragments triggered the generation of highly reactive cytotoxic T lymphocytes (CTL). Moreover, the generation of secondary CTL as induced by allogeneic membrane fragments was preceded by only a marginal cell proliferation. The results obtained are compatible with the concept that serologically defined (SD) antigens alone are capable of triggering alloimmune T cells to differentiate highly reactive secondary CTL.

Animals↗
PubMed1975

The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens.

Helper cell induction to nonparticle antigens in vitro requires the cooperation of T cells and macrophages, but does not occur if the macrophages are allogenic. The reasons for this were investigated. Malfunction of allogenic macrophages was excluded by cultures with their syngenic T cells; suppressor cell induction was excluded by admixture experiments. Thus, T cells and macrophages only cooperated if they were genetically similar. The genetic locus (loci) involved was mapped. Using congenic lines differing only at the H-2 complex, the genetic control of T-macrophage interaction was localized in the H-2 region. Mice with intra H-2 recombinants were used to map the T-macrophage interaction locus in the I-A region of the H-2 complex (formerly known as poly-D, L-ala-poly-L-lys. Recombinants were also used to exclude the presence of another T-macrophage locus either the K, I-B, or I-C, SS-Slp, or D regions of the H-2 complex. Genetic restrictions for T-macrophage interaction in helper cell induction was shown in mice of the H-2-k, d, b, q, s genotypes as well as in H-2 recombinants. The possible mechanisms and significance of this genetic restriction are discussed.

Amino Acids↗