Modulation of T cell differentiation, antigen expression, and radiosensitivity of suppressor cells during late phases of graft-versus-host reactivity.

Suppressor cells generated by inoculation of (B10 X B10.A)F1 hybrid mice with parental spleen cells were characterized during the late period of graft-versus-host (GVH) reactivity, starting on day 14 after parental spleen cell injection and continuing until loss of suppressor activity. The suppressor cell potential was assessed by the ability of spleen cells from the injected F1 mice to suppress the generation of allogeneic cytotoxic T lymphocyte (CTL) responses in vitro by normal F1 responder cells. GVH-associated suppression could be abrogated by anti-Lyt 1, anti-Lyt 2, and anti-Thy 1 plus complement (C') before day 7 postinoculation, and by anti-Lyt 2 and anti-Thy 1 thereafter. However, from day 14 postinoculation on, suppressor cells were insensitive to either of these antibodies. This phase was associated with strong suppressor potential. Subsequent to this period suppressor cells were again sensitive to anti-Thy 1, but not to anti-Lyt 1 or anti-Lyt 2 plus C'--and at the same time they decreased in suppressor activity. Moreover, during the period of resistance to anti-T-cell antibodies plus C', suppressor cells were not killed by anti-asialo GM1 plus C'; were nonadherent to Sephadex G10, and were enriched by nylon-wool passage. In the course of GVH reactivity, suppressor cells alternated in sensitivity and resistance to 500 rads and once went through a brief period of resistance to 2000 rads that was associated with strong suppression and occasionally with mortality. The kinetics of these changes in cell surface phenotype and radiosensitivity were found to vary, coinciding with the strength of the suppression, but the sequence of these events was always the same. During the entire period of GVH reactivity, suppression was mediated by parental cells.