Lymphocyte subpopulations in man: induction of cytotoxic T lymphocytes in vitro by allogeneic B and T cells

Testing B and T cells as allogeneic stimulators of cytotoxic T lymphocytes in primary as well as secondary in vitro cultures, reveals that fresh, nonactivated B cells isolated from peripheral blood have an enhanced cytotoxic T cell stimulating capacity compared to T cells, although target determinants are present both on B and T cell blasts. Similarly, the capacity of T and B cells to stimulate proliferation in MLC is also quantitatively different. These results are in accordance with the hypothesis concerning the in vitro generation of alloreactive cytotoxic T lymphocytes, which postulates concurrent stimulation by strong lymphocyte activating determinants and target determinants for the generation of cytotoxic effector T lymphocytes, as both determinants are simultaneously found on B lymphocytes. Three cell experiments performed by coculturing allogeneic stimulating B and T cells with responding T cells show that strong lymphocyte activating determinants found on B cells enhance the cytotoxicity against target determinants on cocultured B cells but not on cocultured T cells, indicating qualitative differences between target determinants on B and T cells with respect to specific CTL stimulating capacity. Furthermore, primed resting CTLs in secondary cultures could unspecifically be restimulated by third party B cells or pokeweed mitogen. These results are the basis for a hypothesis concerning activation of CTLs, postulating nonspecific triggering of cytotoxic precursor cells by lymphocyte activating properties intrinsic to target determinants (TD) on B cells, preferentially activating clones of cytotoxic cells. The clonal proliferation is further unspecifically amplified by products of the T cell recognition of strong lymphocyte activating determinants (LAD).