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Biomedical subjects

M L Thoman

Publications and source records attributed to M L Thoman.

42 records · Page 3Linked to original sources

Fc fragment activation of T lymphocytes. I. Fc fragments trigger Lyt 1+23- T lymphocytes to release a helper T cell-replacing activity.

Fc fragments of human IgG stimulate both proliferation and polyclonal antibody formation by B lymphocytes. T lymphocytes, although not proliferating in response to Fc fragments, are triggered to produce a T cell-replacing factor, which substitutes for T cells in the Fc fragment-induced polyclonal response. The factor is produced within 24 hr after Fc stimulation. Neither Fab fragments nor whole IgG have the capacity to stimulate the release of this activity. This material is a product of Lyt 1+23-, Ia-T lymphocytes and requires Ia+ adherent accessory cells for production. The role of the accessory cell is to process the Fc fragments to biologically active 14,000-daltons subfragments, which directly trigger T cells to factor production. This material has been called (Fc)TRF to distinguish it from other T cell factors.

Animals↗

Regulation of the immune response. I. The potentiation of in vivo and in vitro immune responses by Fc fragments.

Fc fragments derived from human and murine Ig were found to be potent adjuvants when administered with antigen. Both the in vivo and in vitro anti- sheep erythrocytes (SRBC) responses were significantly enhanced by Fc fragments. The adjuvant effect was shown to be extremely dependent upon the dose of antigen used, with the greatest enhancement occurring when suboptimal doses of antigen are employed. The anti-genicity of the Fc molecule was not related to its adjuvanticity because homologous Fc was as potent an adjuvant as heterologous Fc. Moreover, human Fc fragments enhanced anti-SRBC responses in mice which were tolerant to human gamma globulin.

Adjuvants, Immunologic↗

Activation of T lymphocytes by the Fc portion of immunoglobulin.

T lymphocytes are stimulated to release T-cell-replacing factors in response to Fc fragments of human IgG, Lyt 1+23- T cells are directly triggered to factor production by Fc subfragments, derived from intact Fc fragments by macrophage-dependent enzymatic cleavage. These factor(s) replace T cell function in two Fc-mediated immune responses; induction of polyclonal antibody synthesis, and potentiation of anti-SRBC responses.

Animals↗

Cellular requirements for generation of thymocyte stimulatory factor and characterization of its target cell.

The cellular requirements for the generation of thymocyte stimulatory factor, TSF, were defined, and the target cell for its activity was in part characterized. TSF production, which is triggered by concanavalin A stimulation of murine spleen cells, requires both an Lyt 1+23- cell and an Ia+ non-T accessory cell. The Ia+ cell does not bear surface Ig, is not killed by treatment with antithymocyte sera and C, and is partially depleted by Sephaadex G-10 filtration. TSF-augmentation of the thymocyte mitogenic response to Con A requires Lyt 1+, Ia- thymocytes, which are present in both the cortisone-sensitive and resistant populations. The relationship between TSF and other activities produced by Con A activation of spleen cells is discussed.

Animals↗

Polyclonal activation of murine B lymphocytes by Fe fragments. II. Replacement of T cells by a soluble helper T cell-replacing factor (TRF).

Fc fragments of human gamma-globulin stimulate T cell-dependent polyclonal antibody responses in murine splenic B cells. The T cell signal can be delivered by a soluble T cell-replacing factor, derived by concanavalin A stimulation of spleen cells. TRF interacts directly with responding B cells and appears to provide the second, differentiative, trigger that initiates the polyclonal response. TRF is maximally active even if added at 24 hr after Fc and does not alter the response kinetics. Although macrophages are requird for the polyclonal activation of B cells in intact spleen cell cultures, they are not necessary for the delivery of the TRF signal to B cells.

Animals↗

Regulation of the immune response. II. Characterization of the cell population(s) involved in the Fc fragment-induced adjuvant effect.

Fc fragments derived from human and murine Ig have been shown to possess adjuvant properties. The spleen cell population(s) affected by the Fc fragments is the T lymphocyte. That Fc fragments do not act directly on the B lymphocyte was shown by the fact that in a system where T cell help was substituted for by TRF and using TI antigens, no adjuvant effect was observed. The adjuvant signal provided by the Fc fragments is needed early in the culture period, because it was reduced by approximately 50% when delayed by 24 hr. When the addition of Fc was delayed by 72 hr, the antibody response was not significantly increased over the culture that received antigen only.

Animals↗