CELLULAR IMMUNOLOGY 130,257-270 (1990) Inhibition by Anti-CD2 Monoclonal Antibodies of Anti-CD34nduced T Cell-Dependent B Cell Activation WILLIAM STOHL* AND MARY K. CROW? *Department of Medicine, Division of Rheumatology and Immunology, University of Southern California School of Medicine, Los Angeles, Calijornia 90033; and TDepartment of Medicine, The Hospital for Special Surgery and The New York Hospital-Cornell University Medical College, New York, New York 10021 Received August 28. 1989; accepted June 18, 1990 Anti-CD3 mAb can activate T cells to help in B cell activation as detected by late events, such as maturation of B cells into Ig-secreting cells (IgSC), or by early events, such as B cell surface expression of the activation marker CD23. Two different anti-CD2 mAb each inhibited anti- CD3-induced T cell-dependent B cell activation in a dose-dependent fashion. Neither irradiation of the T cells prior to culture nor depletion of CD8+ cells abrogated the inhibitory effects of anti- CD2 mAb. Despite the ability of these anti-CD2 mAb to inhibit anti-CD3-induced IL2 production, addition of exogenous IL2 to anti-CD2 mAb-containing cultures could not fully reverse the in- hibitory effectson IgSC generation. Furthermore, addition of various combinations of ILI, IL2, IL4, and IL6 or crude PBMC or monocyte culture supernatants also could not reverse anti-CDZ driven inhibition. In T cell-depleted cultures, anti-CD2 mAb had no effect on the ability of IL4 to induce B cell CD23 expression, confirming that anti-CD2 mAb had no direct effect on B cells. However, in cultures containing T + non-T cells, anti-CD2 mAb did partially inhibit IL4induced B cell CD23 expression. Taken together, these observations demonstrate that certain CD2 ligands can modulate T cell-dependent B cell activation by a mechanism which, at least in part, involves a direct effect by the CD2 ligand on the T cell itself. o 1990 Academic press, hc. INTRODUCTION In the context of self-MHC products, antigen will specifically interact with the TCR on the T cell surface and trigger activation of those antigen-specific T cells. To study this activation process, one should ideally choose a population of resting T cells with known antigen specificity. However, the frequency of resting T cells reactive with any given antigen is too low to operationally permit such a study. Nevertheless, resting T cells in bulk can be activated by mAb directed against public epitopes of the TCR (cross-reactive idiotopes or framework determinants) or against surface CD3 ( l-4), a complex of at least four or five different subunits in intimate, but noncovalent, as- sociation with the TCR (5- 10). Thus, anti-TCR and anti-CD3 mAb may mimic phys- iologic activation in that they interact with T cells only via the CD3/TCR complex. Such mAb can induce T cell help in B cell activation as measured either by generation of Ig-secreting cells (IgSC)’ or by B cell expression of the activation antigen CD23 (BLAST-2) ( 1 l- 13). ’ Abbreviations used: IgSC, Ig-secreting cells; sIg, surface lg. 257 0008-8749/90 $3.00 Copyright 0 1990 by Academic Press, Inc. All rights of reproduction in any form reserved.