THE B7 ADHESION MOLECULE IS EXPRESSED ON ACTIVATED HUMAN T-CELLS - FUNCTIONAL INVOLVEMENT IN T-T CELL-INTERACTIONS

The B cell antigen B7 delivers a strong co-stimulatory signal for the activation of T cells by binding to its ligands CD28 and CTLA4. Here w e demonstrate the surface expression of the B7 molecule on activated h uman T cells in vitro and under certain conditions in vivo and its fun ctional importance in T-T cell interactions. B7 was detected by flow c ytometry on antigen-specific CD4+ and allospecific CD8+ cloned T cells from different donors with anti-B7 monoclonal antibody (mAb) or a sol uble CTLA4-Cgamma1 chimera molecule and by reverse transcription-polym erase chain reactions. The expression of B7 was up-regulated following restimulation of the T cell clones and peaked after 7-9 days. Moreove r, we show that the B7 molecule on T cells is functionally involved in T-T cell interactions: mAb to CD28 and the CTLA4-Ig fusion protein co uld inhibit the proliferation of specific T cell clones in response to T cells as antigen-presenting cells (APC) or the proliferation of per ipheral blood mononuclear cells in a primary allostimulation with acti vated T cells as stimulator cells. Finally, we found that B7 can be ex pressed on freshly isolated circulating T cells since in a preliminary study with a limited number of patients, B7 was present on a subset o f CD3+ cells. B7 was expressed on activated T cells (CD4+ and CD8+) of certain human immunodeficiency virus (HIV)-infected individuals (0.5- 20% B7+CD8+ cells) or some patients with autoimmune diseases whereas C D3+ cells of healthy individuals did not express B7. The coexpression of major histocompatibility complex class II molecules and B7 may be r elevant for the capacity of activated T cells to function as APC. The expression of B7 on T cells in vivo in autoimmune diseases and in HIV infection may be important for a better understanding of these disease s.