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.