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Biomedical subjects

M Feldmann

Publications and source records attributed to M Feldmann.

At least 415 records · Page 23Linked to original sources

Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. I. Studies with 2,4-dinitrophenyl conjugates in vitro.

The effect of different degrees of conjugation of levan, dextran, pneumococcal polysaccharide SIII and the copolymer of D-glutamic acid and D-lysine with the 2,4-dinitrophenyl determinant (DNP) on the immunogenic and tolerogenic capacity of its haptenic conjugates was investigated in vitro. A strikingly uniform effect of hapten conjugation was observed despite the marked difference in the mol. wt. and structure (branched or linear) of the carrier molecules. Regarding the anti-DNP response, low density conjugates were immunogenic but not tolerogenic (even at high doses), higher conjugates were both, depending on concentration, while very high density conjugates were only tolerogenic. These results confirm and extend earlier findings made with DNP conjugates of polymeric flagellin and indicate the probable generality of this principle. Together with parallel in vivo studies (Eur. J. Immunol. 1975. 5:541), they reaffirm the importance of epitope density in the discrimination between immunity and tolerance.

Animals↗

The role of macrophages in the generation of T helper cells. III. Influence of macrophage-derived factors in helper cell induction.

Helper cell induction to soluble or particulate antigens in vitro requires the cooperation of T cells and macrophages. A direct contact between macrophages and T cells is not obligatory for this cooperation and factors released from macrophages are as effective in activating T cells as the cells themselves. Two different types of macrophage-derived factors where found. The supernatant obtained from purified macrophages incubated with antigen for several days generates helper cells in absence of macrophages or additional antigen, but only if obtained from macrophages which were identical at the I-A subregion of the H-2 complex as the T cells. This factor was called genetically related macrophages factor (GRF). The other factor(s), which is present in the supernatant obtained from macrophages incubated for several days without antigen, replaces macrophages only if the antigen is particulate. This factor(s), called nonspecific macrophage factor (NMF) is not restricted genetically and is also obtained from allogeneic macrophages. The importance of both these factors in helper cell induction is discussed.

Animals↗

Conditions for inducing T helper cells in vitro.

Lymphoid cells of CBA mice were triggered to act as specific helper cells by incubation with protein antigen (usually keyhole limpet haemocyanin (KLH)) in Marbrook cultures in vitro. After optimum priming, these helper cells, at optimal numbers, stimulated B cells (from unprimed spleens) to respond to trinitrophenyl-KLH in vitro. The in vitro-induced helper cells were carrier-specific. B cell depletion before helper cell induction increased the efficiency of helper cell induction and thus provided further proof of the T-cell nature of in vitro helper cells. Heterogeneity within T helper cell precursors is suggested on the basis of differences in antigen dose requirements of precursor cells in cortisone-resistant thymocytes, spleen, or lymph nodes.

Animals↗