Immunosuppression in Man: Suppression by Macrophages Can be Mediated by Interactions with Regulatory T Cells

Abstract Previous data from this laboratory indicated that profound defects of in vivo and in vitro T cell function noted in some patients with fungal infection reflected the presence of immunosuppressive forces. Investigation of the cellular interactions required for this immunosuppression to become manifest revealed the following. Patients' macrophages liberated, in vitro, a soluble material (SM)3 capable of inhibiting the blastogenic response of normal T cells to mitogens and antigens. However, not all T cells were equally susceptible to its suppressive effect. Incubation of normal PBMC in culture fluid for 7 days yielded a population of cultured T cells whose reactivity could not be inhibited by SM. Binding studies indicated that this “resistance” did not reflect any gross alterations in the ability of cultured T cells to interact with SM. Rather, it reflected the functional deletion of a subpopulation of T cells required for SM to mediate its suppressive effect. This was demonstrated by the finding that in the presence of low density, fresh, autologous T cells, SM was capable of suppressing the reactivity of cultured T cells. Similar interactions between SM and low density T cells appeared to be required for SM to inhibit T-dependent responses among fresh noncultured PBMC. Thus, removal of low density T from fresh normal PBMC yielded high density T whose reactivity was not suppressed by SM. These studies are interpreted as indicating that immunosuppression in the patients studied does not reflect direct interactions between suppressive macrophages and responding T cells. Instead, it represents an indirect interaction whereby macrophages may generate or potentiate active suppressive T cells.