Multiple sites of post-activation CD8+ T cell disposal.

Antigen-triggered activation of T cells leads to a sequence of differentiation steps including up-regulation of activation markers, blast formation, proliferation, delivery of effector functions, and ultimately apoptosis. It is still controversial in which anatomical site activation-induced apoptosis and elimination of T cells occur. To address this question, we used mice transgenic for a T cell receptor (F5) specific for an influenza virus nucleoprotein peptide (NP68) presented on the major histocompatibility complex H-2 Db molecule. Accumulation and apoptosis of T cells was studied using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling in situ combined with immunohistology after intraperitoneal injection of the cognate peptide into F5 mice which are wild type or deficient for Rag-1. After 4 days of peptide treatment, large perivascular infiltrations of CD8+ cells were observed in liver, lung, and kidney of F5 mice. CD8+ cell numbers were also increased in skin and small intestine, but not in brain or heart muscle of peptide-treated animals. The infiltrating CD8+ cells show an increased percentage of apoptosis in liver, lung and, most strikingly, the kidney. These data suggest that in the F5 system, T cell 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 cells.