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.
Wack
A
A
Division of Molecular Immunology, National Institute for Medical Research, London, GB.
Corbella
P
P
Harker
N
N
Crispe
I N
IN
Kioussis
D
D
D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002470:Cell Survival; D053938:DNA Fragmentation; D018398:Homeodomain Proteins; D007421:Intestine, Small / Q000166:cytology; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D018398:Homeodomain Proteins; D011506:Proteins; C064658:RAG-1 protein