SELECTIVE INCREASE IN CD4-POSITIVE GRAFT-INFILTRATING MONONUCLEAR-CELLS AMONG THE INFILTRATES IN CLASS-I DISPARATE KIDNEY GRAFTS UNDERGOINGREJECTION

Long-term tolerance to kidney allografts across a two-haplotype class I disparity is uniformly induced in miniature swine with a short cours e of cyclosporine (CsA). In the absence of CsA, all recipients acutely reject kidney allografts within 2 weeks, Previous experiments have sh own that graft-infiltrating mononuclear cells (GIG) migrate to the all ograft in both CsA-treated and untreated animals. To evaluate the corr elation between GIC phenotype and the clinical status, infiltrating ce lls were examined by flow cytometry, using selective gating to disting uish them from other renal cells, GIC from tolerant and rejector anima ls were mostly mature T cells, with 84% CD8(+) cells, which consisted of 68% CD8(+)/CD4(-) and 16% CD8(+)/CD4(+) cells, This cellular phenot ype was, however, markedly different from that of peripheral blood lym phocytes, suggesting a selective migration of cells into the graft, Th is selective process counterselected the CD3(+)/CD2(-) subset of GIC, which was never found in the graft, The distribution of GIC subsets wa s initially comparable in tolerated and rejected kidneys, but the CD4 single-positive subset then increased specifically in the allograft de stined to rejection, The absence of CD4 single-positive cells in toler ated grafts was unlikely to be due to a direct effect of the CsA, beca use long-term tolerant animals, which received a second kidney without further immunosuppression, also showed no increase in CD4 single-posi tive cells, The fact that CD4 single-positive cells appeared only with in the rejected kidneys, strongly suggests that this cell subset may b e important in mediating immune rejection and supports the hypothesis that the development of tolerance in this model depends on a relative deficit of T-cell help.