Adoptive transfer of a Th2-like cell line prolongs MHC class II antigen disparate skin allograft survival in the mouse.

The MHC class II alloantigen-reactive CD4+ Th2-like cell line, HR2, was established. It was derived from the spleen cells of C57BL/6 (B6) mice immune to an MHC class II-disparate mutant mouse, B6.CH-2bm12 (bm12) which carries the I-Abm12 antigen. This cell line, HR2, secretes IL-4 and IL-10 in an antigen-specific manner, and can also proliferate in an autocrine manner through IL-4. To investigate the in vivo role of this Th2-like CD4+ T cell line in transplantation immunity, an adoptive cell transfer study using the skin allograft system was performed. Skins grafted from bm12 to B6 were rejected at 12.1 +/- 0.6 days in control B6 mice which received no treatment. Whereas skin graft survival was prolonged in B6 experimental mice which had received 2 x 10(7) HR2 cells, 75% of the grafts survived for > 40 days. Moreover, since skin grafts from fully allogeneic third party donor BALB/c mice were rejected at 12.0 +/- 0.4 days by B6 mice which had received the same number of HR2 cells, it was demonstrated that HR2 is involved in the regulation of bm12 skin graft rejection. Furthermore, cytotoxic T lymphocyte (CTL) activity by spleen cells from HR2 transferred B6 mice was not induced even by in vitro secondary stimulation, although CTL activity was induced well in spleen cells of control B6 mice which had rejected the graft. The underlying mechanism has not been fully clarified; however, these results demonstrate that Th2-like CD4+ T cells suppress allograft rejection.