Search PubMed⌕ Search

Biomedical subjects

S S Fairchild

Publications and source records attributed to S S Fairchild.

10 recordsLinked to original sources

T cell-derived glucosteroid response-modifying factor (GRMFT): a unique lymphokine made by normal T lymphocytes and a T cell hybridoma.

Mouse spleen cells and a murine T cell hybridoma, FS6 14.13.1, produce a glucosteroid response-modifying factor (GRMFT) after stimulation with concanavalin A. GRMFT blocks glucosteroid suppression of helper T cell function and the growth of granulocyte/macrophage progenitor cells in vitro. IL 1 also protects helper T cells and myeloid precursors from glucosteroid suppression. This suggests that GRMFT and IL 1 act congruently to ensure that an effective immune response is generated when endogenous glucosteroid levels are elevated. To understand the role of GRMFT in normal immune responses and in disease states characterized by imbalances in the immune system, we began to purify and characterize GRMFT. GRMFT appears to be distinct from other well-characterized T cell-derived factors. GRMFT is larger than IL 2 as determined by gel exclusion chromatography and is completely separated from IL 2 by isoelectric focusing. Furthermore, purified IL 2 does not have GRMFT activity. Purified IL 3 also lacks GRMFT activity, and conditions that inactivate immune interferon have no effect on GRMFT. Thus, GRMFT is different from IL 2, IL 3, and immune interferon. GRMFT also lacks activity in the thymocyte co-mitogenic assay and is therefore different from IL 1. Finally, FS6 14.13.1 reportedly does not produce TRF or CSF, which suggests that GRMFT is different from these molecules as well.

Animals↗

Thymic control of proliferation of T cell precursors in bone marrow.

The activity of T lymphocyte precursors (pre-T cells) in the bone marrow of mice was measured by the concanavalin A response synergy assay. Pre-T cell levels were low in marrow of neonatally thymectomized mice and could be restored to control values by treatment in vivo with an extract of mouse thymus. Levels of activity were also low in aging mice and again could be restored by thymic extract treatment. The most profound fall with aging was in the proliferating pre-T cell compartment as detected by tritiated thymidine suicide; and this compartment was restored by thymic extract treatment. Irradiation to the thymus, with the bone marrow shielded, caused a fall in resting pre-T cells in the bone marrow and a concomitant rise in proliferating cells. These results are consistent with a model of control of pre-T cell maturation in which the thymus senses the number of developing lymphocytes within it and responds to a fall in this number by increasing production of hormone. The hormone acts on resting pre-T cells in the marrow, stimulating some of them to proliferate, leave the bone marrow, and repopulate the thymus.

Aging↗

T-Lymphocyte precursors. I. Synergy between precursor and mature T lymphocytes in the response to concanavalin A.

When mouse bone marrow cells are mixed with cortisol-resistant thymocytes and stimulated in vitro with concanavalin A, the mitogenic response observed is much greater than additive, that is, it is synergistic. Between 94 and 96% of responding cells could be identified as T cells (Thy-1 positive) and of these, 79-100% derived from the cortisol-resistant thymocyte population, not from the bone marrow. Purified macrophages could not replace bone marrow; and marrow depleted of mature T or B cells worked as well as normal marrow. Thus, T and B cells and macrophages were ruled out as the synergizing cell of bone marrow. Nude spleen contained 10 times as many precursors of T cells as did nude marrow and was 10 times better at synergy with cortisol-resistant thymocytes. This implication of the pre-T cell as synergizer was supported by the finding that the synergistic activity of marrow was lost on preincubation, but maintained if the preincubation medium contained thymosin or cyclic AMP. Thus, the ability to enhance the response of relatively mature T cells to Con A is a property of pre-T cells. It is anticipated that this property will allow more detailed studies of T-cell precursor development in mice, and possibly in man.

Animals↗

Mouse B and T lymphocyte responses to purified timothy pollen antigens in vitro.

Purified populations of splenic B and T lymphocytes from LAF mice immunized with a crude extract of timothy pollen (WST) responded specifically to pollen antigens in an in vitro lymphocyte transformation system. The peak lymphocyte transformation response occurred 5 days after a secondary immunization and was the result of T-B cell cooperation in vitro. Wtih two purified pollen antigens as in vitro stimulants we were able to define at least two antigen-specific population of B cells and one population of T cells. These results were confirmed by inhibition studies with a monovalent hapten from WST, Antigen D.

Animals↗

Response of mouse splenic lymphocytes to timothy pollen antigens in a microculture system.

Spleen cells from LAF1 mice were stimulated in a microculture system with T and B cell mitogens or antigens of timothy pollen. Only cells from mice immunized with crude timothy pollen extract (WST) or a major antigen of timothy pollen conjugated to Ascaris (antigen B-Ascaris) responded to timothy antigens in vitro. Optimum responses were obtained at 120 to 144 hr of culture with 5 to 10 mug WST per culture and ranged from three to 10 times greater than cell background. No correlations could be found between the optimum antigen concentration or the maximum response and the immune status of the spleen cell donor. Response could be inhibited by a dialyzable fraction of timothy pollen, antigen D, which is a monovalent form of a major antigen of timothy pollen.

Animals↗

Induction of mouse homocytotropic antibodies to Timothy pollen antigens.

The IgG1 and IgE homocytotropic antibody responses of LAF and C3H mice to timothy pollen antigens are defined. Both mouse strains responded to low doses of crude timothy pollen extract (WST) or a major antigen of timothy pollen coupled to a purified fraction of Ascaris suum (Antigen B-Ascaris). Titers in LAF mice were greater than those in C3H mice. Regardless of the immunogen, antigen B was the major determinant recognized by the homocytotropic antibodies; PCA titers with WST or antigen B for challenge were equivalent and PCA activity could be inhibited by antigen D, a dialyzable fraction of timothy pollen possessing the antigen B determinant in monovalent form. The possible usefulness of antigen D for in vivo and in vitro studies of specific immune suppression of cellular activity is discussed.

Animals↗