MULTIPLE SITES OF POST-ACTIVATION CD8(-CELL DISPOSAL() T)

Antigen-triggered activation of T cells leads to a sequence of differe ntiation steps including up-regulation of activation markers, blast fo rmation, proliferation, delivery of effector functions, and ultimately apoptosis. It is still controversial in which anatomical site activat ion-induced apoptosis and elimination of T cells occur. To address thi s question, we used mice transgenic for a T cell receptor (F5) specifi c for an influenza virus nucleoprotein peptide (NP68) presented on the major histocompatibility complex H-2 D-b molecule. Accumulation and a poptosis of T cells was studied using terminal deoxynucleotidyl transf erase-mediated dUTP-biotin nick end-labeling in situ combined with imm unohistology after intraperitoneal injection of the cognate peptide in to F5 mice which are wild type or deficient for Rag 1. After 4 days of peptide treatment, large perivascular infiltrations of CD8(+) cells w ere observed in liver, lung, and kidney of F5 mice. CD8(+) cell number s were also increased in skin and small intestine, but not in brain or heart muscle of peptide-treated animals. The infiltrating CD8(+) cell s show an increased percentage of apoptosis in liver, lung and, most s trikingly, the kidney. These data suggest that in the F5 system, T cel l disposal after activation occurs in a number of organs. Essentially identical findings were obtained in Rag-1(+/+) and Rag-1(-/-) F5 mice, suggesting that the deletion mechanism did not involve other T or B c ells.