Divergent Tγ cell functions in antigen-induced blastogenesis: facilitory interactions with Tnonγ cells and participation in monocyte- and prostaglandin-mediated suppression

The contribution of T_γ cells, i.e., T cells bearing surface receptors for the Fc portion of IgG, to the immunologic response to antigen has not been assessed in health or disease. We examined the role of T_γ cells in antigen-induced blastogenesis of T cells from healthy subjects and characterized their participation in monocyte- and prostaglandin-mediated suppression. Cell fractions enriched in and depleted of T_γ cells were prepared from nonadherent T cells by preparative resetting with IgG-sensitized ox erythrocytes; antigen-induced blastogenesis was assayed as ³H-thymidine incorporation (³H-TdR), by microculture techniques. Removal of T_γ cells resulted in a Tnon_γ cell fraction whose in vitro response to soluble antigen was a mean 40% ± 8 less than the response of the unseparated T cells from the same donors. Antigen did not induce ³H-TdR in cultures of T_γ cells; however, in cell-mixing experiments, addition of autologous T_γ cells reconstituted the antigen responsiveness of the Tnon_γ cell fraction. Monocytes (MN) added to cell cultures at a ratio known to be suppressive in vitro (MN to T = 1:4) significantly decreased antigen-induced ³H-TdR of unseparated T cells but did not alter the antigen responses of Tnon_γ cells. MN-dependent suppression was abrogated by co-culture with indomethacin. Exogenous prostaglandin E₂, an immunosuppressive cyclooxygenase product of MN, selectively decreased antigen-induced ³H-TdR of cell cultures containing T_γ cells but did not affect antigen responses of Tnon_γ cell fraction. Thus these studies show that MN and their cyclooxygenase products modulate T_γ cells to function in a suppressive mode. This demonstration of divergent T_γ cell functions indicates that the contribution of an expanded T_γ cell population to altered antigen reactivity in disease can be determined only by careful functional studies.