Veto in vivo?

Abstract

The way in which self-reactive cytotoxic T lymphocytes (CTL) are functionally inactivated remains unknown. One possible mechanism is the 'veto' phenomenon, by which specialized cells present incentral lymphoid tissues (bone marrow and thymus), but not in spleen or lymph nodes, are able to suppress the generation (in mixed lymphocyte culture) of alloreactive CTL which recognize alloantigens shared by the stimulator cells and the veto cells ~'2. The crucial event in this system seems to be recognition of the veto cell by the CTL precursor. Thus, in contrast to other kinds of suppressor cells, the veto cell inactivates C T L precursors, not on the basis of its own specificity, but on the basis of theirs. In a syngeneic situation these cells have the properties required to eliminate self-reactive CTL, and their anatomical localization makes sense in terms of this function. Cells may be cultured from foetal thymus which exhibit the veto effect 3, furthermore, in nude mice veto activity is demonstrable in spleen cellsL Any model of repertoire ontogeny in which self-reactive CTL precursors are eliminated in the thymus 5 has difficulty in explaining the presence of alloreactive C T L but absence of self-reactive CTL in nude mice6; if self-reactivity was vetoed in the spleen in athyrnic mice their apparently successful deletion of antiself C T L could be explained. Recent studies have suggested a veto-like effect in immunoregulation, in experiments where the intravenous injection of allogeneic lymphoid cells resulted in the suppression of CTL responses against antigens carried on the immunizing cells. Here, we discuss these experiments and difficulties with their interpretation. In particular, we question whether the analogy with the invitro veto phenomenon described by Miller and colleagues is acceptable. Rammensee and colleagues examined the in-vivo priming requirements for secondary in-vitro CTL responses against single minor histocompatibility antigens. Mice were primed by intravenous injection, and their spleen cells challenged in vitro after five days; C T L were assayed from these cultures. Intravenous injection of 108 viable allogeneic spleen cells failed to prime, However, if the 108 spleen cells were heavily irradiated (with 3 300 R) or depleted of T cells, they then primed effectively 7. These