Signal transduction through crosslinking CD7 and IgM-Fc receptors that inhibits T-cell proliferation.
We have previously suggested a possible involvement of CD7 and/or the putative receptor for IgM-Fc (FcRmu) in the downregulation of T-cell responses to mitogen and alloantigen. In this report, we examined the effect of ligand-receptor interaction upon T-cell proliferation by using anti-CD7 monoclonal antibodies (mAbs) and purified human IgM (HIgM) and showed that crosslinking CD7 and/or FcRmu on T cells resulted in significant inhibition of mitogen- and alloantigen-induced proliferative responses. In most cases, crosslinking of FcRmu alone or together with CD7 receptors on peripheral blood lymphocytes (PBLs) resulted in more potent suppression of T-cell proliferation than that caused by crosslinking CD7 alone. Examination of potential inhibitory mechanisms revealed that crosslinking CD7 and FcRmu does not reduce cell viability or the expression of T-cell markers that are important for T-cell activation or proliferation. However, crosslinking CD7 and/or FcRmu of PBLs significantly reduced phytohemagglutinin (PHA)-induced IL-2 production and rendered PBLs unable to utilize exogenously added human recombinant IL-2 (rIL-2). Further examination of possible signal transduction that might be associated with crosslinking CD7 and/or FcRmu receptors indicated a marked reduction in the magnitude and duration of intracellular calcium (Ca++)i released in response to PHA. These findings suggest that crosslinking CD7 and FcRmu inhibits T-cell activation and proliferation by a calcium-dependent mechanism that inhibits IL-2 production and/or utilization.
Emara
M
M
Department of Pathology and Laboratory Medicine, East Carolina University School of Medicine, Greenville, North Carolina.
Carroll
R G
RG
D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D011961:Receptors, Fc; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D007375:Interleukin-1; D007376:Interleukin-2; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D002118:Calcium