REJECTION OF H-Y DISPARATE SKIN-GRAFTS BY MONOSPECIFIC CD4(- NO REQUIREMENT FOR CD8(+) T-CELLS OR B-CELLS() TH1 AND TH2 CELLS )

We wished to determine whether CD4(+) T cells could reject a skin graf t that was discordant for a single minor transplantation Ag in the abs ence of CD8(+) T cells or Ab, Transgenic Al(M) mice were constructed t hat express the rearranged V beta 8,2 and V alpha 10 TCR genes from a T cell clone that is specific for the male Ag (H-Y) in the context of H2-E-k. In addition, the RAG-1(-/-) background was bred onto these mic e to eliminate any endogenous TCR rearrangements, As expected, clonal deletion was found to be complete in the thymus of male Al(M) x RAG-1( -/-) mice, while only CD4+ T cells were positively selected and found in the periphery of females. Female Al(M) x RAG-1(-/-) mice were able to rapidly reject (in <14 days) male (but not female) skin grafts in a CD4-dependent fashion. After multiple grafts, it was confirmed that n o CD8(+) T cells or surface Ig(+) B cells were present. An immunofluor escent analysis of spleen cells after grafting showed that the majorit y of T cells expressed activation markers (CD44, CD25, and intracytopl asmic IL-2) and a significant proportion were making IFN-gamma and IL- 4, Surprisingly, the transfer of either Th1 or Th2 CD4(+) T cell lines from these mice into T cell-depleted recipients was sufficient to cau se a specific rejection of male skin.