Cytotoxic T cells with reciprocal antigenic peptide presentation function are not generally resistant to mutual lysis.

Cytotoxic T cells normally express major histocompatibility complex class I molecules, to which their T cell antigen receptors are restricted. Therefore, a single cytotoxic T cell can not only act as a cytolytic effector cell, but also as an antigen-presenting cell for other cytotoxic T cells of the same or a different clone. In the present paper, we used a murine cytotoxic T cell clone, 10BK.1, recognizing the ovalbumin-derived peptide OVA257-264 in combination with H-2Kb to investigate the consequences of reciprocal antigen presentation by these cytotoxic T cells. These cells proliferate after incubation with the relevant peptide in the absence of added accessory cells, indicating reciprocal antigenic peptide presentation by the cytotoxic T cell. We found that reciprocal lysis of these cells was dependent on the time point of incubation with antigen. We did not observe reciprocal lysis of cytotoxic T cells used 30 days after the last restimulation with antigen. In contrast, 10BK.1 cells used two days after the last restimulation showed an increased capacity for reciprocal lysis. The lytic capacity decreased with time after restimulation. Reciprocal lysis of 10BK.1 cells depended on reciprocal peptide presentation by at least two 10BK.1 cells. Recognition of the antigenic peptide, together with class I molecules on the surface of classical syngeneic target cells did not induce lysis of freshly stimulated 10BK.1 cells, suggesting that reciprocal lysis was not just a consequence of re-activation of the cytotoxic T cells. Reciprocal destruction of freshly activated 10BK.1 cells proceeded independent of CD95/CD95 ligand. Despite an increased secretion of tumour necrosis factor-alpha by 10BK.1 cells on day 2 after antigen stimulation, compared with cells on day 30 after stimulation, tumour necrosis factor-alpha was not responsible for the reciprocal destruction of freshly stimulated 10BK.1 cells. Lysis of preactivated 10BK.1 cells was independent of autocrine interleukin-2 production by the cytotoxic T cells, but interleukin-2 was required for optimal priming of cytotoxic T cells for reciprocal lysis.