A human suppressor T-cell factor that inhibits T-cell replication by interaction with the IgM-Fc receptor (CD7).
We have previously described the induction of human suppressor T cells from fresh peripheral blood lymphocytes of a kidney transplant recipient by in vitro stimulation with an autologous irradiated antidonor CTL line (EE-1) grown from a biopsy of the patient's own renal allograft. The induced T cells (designated TsEE) were shown to inhibit the in vitro generation of proliferative and cytotoxic responses of autologous T cells and nonautologous T cells that shared HLA-B7 with TsEE cells. Stimulation of TsEE cells by the autologous irradiated inducer line (EE-1) produced soluble factors (designated TsEEF) that similarly inhibited autologous and nonautologous T-cell responses to alloantigens and mitogens, but in a non-HLA-restricted manner. In this study, we examined the functional interaction of TsEEF with various cells surface receptors. TsEEF specifically inhibited the proliferation of stimulated and transformed T cells expressing CD7, a putative receptor for IgM-Fc (FcRmu). Blocking or capping of CD7-FcRmu determinants on responder T cells by pretreatment with IgM or anti-CD7 monoclonal antibodies (3A1, HuLy-m2) abrogated TsEEF activity. Conversely, pretreatment of T cells with TsEEF significantly reduced their binding of IgM and HuLy-m2. TsEEF was demonstrated not to be IgM or IgG, and its activity was not removed by preabsorption with IgM or IgG; however, its activity could be competitively inhibited by coculture with IgM. By cocapping experiments and studies utilizing CD7- (Hut-78) and CD7+ (HSB, Molt-4) T-cell lines. TsEEF activity did not appear to involve interactions with other T-cell or non-T-cell surface receptors. These findings suggest a novel role for FcRmu-CD7 T-cell surface receptors in binding certain soluble T-cell factors that result in the inhibition of T-cell replication.
Emara
M
M
Department of Pathology, Duke University, Durham, North Carolina 27710.
Baldwin
W M
WM
Finn
O J
OJ
Sanfilippo
F
F
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D011961:Receptors, Fc / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D005456:Fluorescent Dyes; D011961:Receptors, Fc; D013491:Suppressor Factors, Immunologic; C035311:immunoglobulin M receptor