Cd4+ T Cells Are Able to Reject Class I Disparate Allografts1

Abstract

The ability of CD4+ T cells to reject class I mismatched skin allografts remains controversial. In this study, we compare the ability of CD4+ T cells to reject class I disparate skin grafts differing by either a single class I allelic disparity or only 3 amino acids encoded by the H-2K locus. We demonstrate that skin grafts across a full H-2K allelic disparity, but not across a disparity of only three amino acids are efficiently rejected by CD4+ T cells. This observation is consistent with the possibility that peptides derived from allogeneic class I molecules generated through the major histocompatibility complex (MHC) class II antigen processing pathway can be recognized by host CD4 T cells and lead to rejection of class I mismatched skin grafts. The availability of peptides derived from allogeneic MHC class I molecules for presentation by host MHC class II may determine the efficiency of rejection of class I mismatched allografts by CD4+ T cells. Thus, class I mismatched allografts can be rejected by CD4+ T cells provided that host and donor MHC class I molecules are sufficiently disparate to activate CD4+ effectors.

Induction of Alloreactive CD4 T Cell Tolerance in Molecular Chimeras: A Possible Role for Regulatory T Cells

“…More recently, we have shown that molecular chimerism can be induced in hosts receiving nonmyeloablative conditioning and similarly results in tolerance to K b disparate skin grafts (14). Both CD8 and CD4 T cells are able to reject MHC class I disparate skin grafts (15,16). Therefore, in order for molecular chimeras to accept K b disparate skin grafts, both CD8 and CD4 T cells that recognize K b through the direct and indirect pathways must be tolerized.…”

“…All cell surface staining and flow cytometry were performed as previously described (15,22). Abs specific for H-2K b (AF6 -88.5), H-2D q (KH117), V␤10 TCR (B21.5), CD4 (L3T4), CD8 (52-6.7), CD11b (Mac-1, M1/70), Gr-1 (RB6-8C5), CD11c (HL3), CD25 (PC61), TCR ␤-chain (H57-597), and B220 (RA3-6B2) were obtained from BD Pharmingen.…”

Induction of Central Deletional T Cell Tolerance by Gene Therapy

“…All cell surface staining and flow cytometry were performed as described previously (22,23). The hybridoma secreting the BM3.3 anticlonotypic Ab Ti98 was kindly provided by Dr. A. L. Mellor (14).…”

Induction of Central Tolerance by Mature T Cells

“…Insofar as we were able to detect K b only on the surface of T cells, we suggest that if intact K b is transferred to other cell types, it occurs at a low efficiency. Nevertheless, we have previously shown that K b disparate skin grafts can be rejected by alloreactive CD4 T cells that recognize peptides derived from K b presented on donor or host MHC class II (13). To prevent rejection through this pathway, T cells that recognize K b -derived peptides in the context of MHC class II must also be tolerized by the transferred alloantigen-expressing T cells.…”

“…All cell surface staining and flow cytometry were performed as described previously (12,13). Expression of K b on cell surface was evaluated, as described previously (7).…”