Allograft rejection in athymic nude rats by transferred T cell subsets. II. The response of naive CD4+ and CD8+ thoracic duct lymphocytes to an isolated MHC class I disparity.

ABSTRACT

Athymic PVG-rnu/rnu (RT1c) rats were grafted with skin bearing isolated MHC disparities 7-14 days in advance of cell transfer. The ability of naive CD4+ or CD8+ thoracic duct lymphocytes to induce rejection was assessed by adoptive transfer of one or both T cell subsets into nude recipients bearing congenic PVG.r1 (MHC class I-only disparity, Aa) or PVG.r19 (class I and II-only disparity, Aa B/Da) skin grafts. Recipients of purified CD4+ TDL always rejected r19 allografts, whereas CD8+ TDL were ineffective against this class I + II difference. Neither the injection of CD4+ TDL nor CD8+ TDL alone resulted in destruction of r1 skin grafts. However, rejection of r1 tissue was observed in 63% of cases (19/30) when both CD4+ and CD8+ TDL were present in the nude recipients. Rejection of r1 skin was also induced in some recipients when CD8+ TDL were transferred 8 weeks in advance of CD4+ TDL. In contrast, sequential transfer in the reverse order apparently induced tolerance in the CD4+ population--i.e., surviving r1 skin grafts on 8 week CD4+ T cell-reconstituted nude recipients were not rejected following the subsequent transfer of CD8+ TDL. We conclude that CD4+ T cells were required for rejection of both class I and class II differences. In the presence of a class II difference, CD4+ T cells function autonomously to initiate both the inducer and effector stages of rejection. When the disparity is confined to class I, CD8+ T cells are required (probably at the effector stage) but are dependent on CD4+ T cells for help. There was no evidence of CD4+ effector T cells that could recognize class I directly within the graft.