GENERALIZED LOSS OF TcR BY GRAFT INFILTRATING T CELLS

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108 Introduction: The acute rejection of DBA/2→C57B1/6 heterotopic cardiac allografts is characterized by an intense leukocytic interstitial infiltrate. During histologic analyses of allograft infiltrates, we noted that T cells were difficult to detect with the 145-2C11 mAb, which recognizes the epsilon chain of the CD3 complex, and we investigated this further. Methods and Results: The allograft infiltrates react with several other T cell-related mAbs, including a Thy 1.2 reactive mAb (30-H12), a CD4 reactive mAb (GK 1.5), and a CD8 reactive mAb (Lyt2). The 145-2C11 mAb readily detected T cells in simultaneously stained spleens from the allograft recipients. Intragraft T cells, but not splenic T cells, were also difficult to detect with mAbs directed at other components of the TcR, including the H57-597 mAb (anti-αβTcR), the TR310 mAb (anti-Vβ7), and the YCD3-1 mAb (undifined CD3 epitope). To further investigate this phenomenon, naive C57B1/6 splenocytes, which readily react with antibodies directed at the CD3 complex, were transfused into C57B1/6 SCID mice. These mice were transplanted with DBA/2 cardiac allografts, and 10 days later the spleens and grafts were retrieved for evaluation of histologic reactivity with anti-TcR antibodies. We observed that the spleens of these SCID mice reacted with mAbs directed at Thy1, CD4, CD8 and CD3. Large numbers of lymphocytes also accumulated in the grafts of the mice, and these cells reacted with mAbs directed at Thy1, CD4, CD8, but not CD3. Thus, most of the CD4+, CD8+ and Thyl+ splenocytes that migrated into murine cardiac allografts did not display histologically-detectable TcR molecules, whereas TcR were well-displayed by splenocytes that migrated into the spleen. Conclusion: Most T cells present in rejecting allografts appear to lose their TcR. Since limiting dilution studies have shown that antigen-specific T cells represent a small fraction of T cells that accumulate at a graft site, we further conclude that this TcR loss must occur in a antigen-nonspecific manner, and perhaps occurs when TcRs do not engage specific MHC-associated allopeptides at a site of inflammation. Future transfer studies using donor-reactive TcR transgenic T cells will address this issue directly.