DOWN-REGULATION OF T-CELL RECEPTOR EXPRESSION BY CD8(+) LYMPHOCYTES IN KIDNEY ALLOGRAFTS

Allospecific CD8(+) T lymphocytes are an important component of the ce llular response in allograft rejection. These cells recognize and enga ge MHC class I antigens, leading to allospecific cytolytic responses a nd graft rejection. In mouse kidney allografts that survive to 3 wk af ter transplantation, we noted that the majority of CD8(+) cells do not express surface alpha/beta T cell receptor alpha/beta(TCR), gamma/del ta TCR, or CD3. However, these CD8(+)TCR(-) cells did express surface markers characteristic of T cells, including Thy 1.2, CD2, and CD5. In addition, the CD8(+)TCR(-) cells expressed mRNA for TCR V beta gene f amilies, and nearly half stained positive for cytoplasmic V beta 8 pro tein, suggesting that they are T cells that have downregulated alpha/b eta TCR protein expression from their cell surfaces. When these surfac e TCR-cells were isolated from kidney allografts by flow cytometry and cultured in the presence of either allogeneic or syngeneic stimulator s, nearly 100% of cells reacquired normal levels of alpha/beta TCR exp ression with disproportionate usage of V beta 8 chains, After recovery of their surface TCR expression, the CD8(+)TCR(-) population demonstr ated strong alloreactivity in culture. These results suggest that the substantial number of CD8(+)TCR(-) cells found in long-term surviving mouse kidney allografts are alpha/beta-T cells that have downregulated their cell surface expression of TCR, While in other systems this phe notype may identify cells that have engaged antigen, our results indic ate that loss of TCR expression by CD8+ kidney graft-infiltrating cell s may not depend on antigen engagement and that elements in the microe nvironment of the kidney graft play a key role in this process. Factor s that modulate expression of TCR by graft-infiltrating lymphocytes ma y have an important role in regulating rejection responses.