ANTIGEN-PRESENTING T-CELLS INDUCE THE DEVELOPMENT OF CYTOTOXIC CD4(-CELLS .1. INVOLVEMENT OF THE CD80-CD28 ADHESION MOLECULES() T)

The development of cytotoxic CD4(+) T lymphocytes that can kill target cells in a MHC class II-restricted manner was evaluated by comparing different APCs. B-lymphoblasts (B-LCL) pulsed with the superantigen st aphylococcus enterotoxin B or allogeneic B-lymphoblasts induce CD4(+) T cells without cytotoxic activity, In contrast, superantigen-pulsed, MHC class II+ T cell blasts or allogeneic T cell blasts preferentially induce the development of specific, MHC class Ii-restricted CD4(+) cy totoxic effector cells. CD4(+) T cell clones generated with T or B cel l blasts as APCs (T- or B-APCs) differ in their cytolytic potential, b ut secrete a similar cytokine pattern. Our data implicate that activat ed T-APCs preferentially induce a cytotoxic, CD8(+) and CD4(+) T cell response. Because the density of CD80 expression is lower on activated T-APCs than on B-APCs, we studied the involvement of CD28 and CD80 ad hesion molecules in the generation of CD4(+) CTLs. Partial blockade of the CD80 molecule with a CTLA4-Ig fusion protein and with specific an ti-CD80 mAbs on B-APCs enhanced the generation of CD4(+) CTLs. Specifi c anti-CD86 mAbs, on the contrary, had no effect on the generation of CD4(+) CTLs. In contrast, stimulation of CD28, the CD80 counter-recept or, with a cross-linked B7-Ig fusion protein or with an anti-CD28 mAb, inhibited the generation of CD4(+) CTLs. Thus, a reduced interaction between CD80 and CD28 may be relevant for the induction of CD4(+) CTLs . This shows a new and not yet described function of these adhesion mo lecules. This induction of a cytotoxic immune response by T cells as A PCs may be relevant for the anticlonotypic regulation of T cells and f or the depletion of CD4(+) T cells in HIV infection.