The role of B7 molecules in the cell contact-mediated suppression of T cell mitogenesis by immunosuppressive macrophages induced with mycobacterial infection

Abstract

SUMMARY We found previously that immunosuppressive macrophages (Mφs) induced by Mycobacterium intracellulare infection (MI-Mφs) transmitted their suppressor signals to target T cells through cell contact with target T cells. In this study, we examined what kinds of Mφ surface molecules are required for such cell–to–cell interaction. First, it was found that a B7-1-like molecule (B7–1LM) recognizable with one of three test clones of anti-B7-1 monoclonal antibodies (mAbs) was required for expression of the Mφ suppressor activity. Neither anti-B7-2, anti-ICAM-1, nor anti-VCAM-1 mAb blocked the Mφ suppressor activity. Second, MI-Mφs increased the expression of B7–1LM in parallel with the acquisition of the suppressor activity. Moreover, MI-Mφs bound with target T cells in a B7–1LM-dependent fashion. Third, mAb blocking of CTLA-4 on target T cells did not reduce the suppressor activity of MI-Mφs, suggesting the role of a putative molecule on target T cells other than CTLA-4 as the receptor for B7–1LM of MI-Mφs. Fourth, concanavalin A (Con A) stimulation of MI-Mφs was needed for effective cell contact with target T cells and subsequent expression of the suppressor activity of MI-Mφs. Fifth, the Con A-induced increase in the suppressor activity of MI-Mφs was inhibited by KN-62 but not by herbimycin A, H-7, nor H-88, indicating that Con A-induced up-regulation of MI-Mφ function is mediated by calmodulin-dependent protein kinase II or ATP/P2Z receptors, but independent of protein tyrosine kinase, protein kinase C, and protein kinase A. These findings indicate that a B7/CTLA-4-independent mechanism is needed for the transmission of the suppressor signals from MI-Mφs to target T cells.