Oct 23, 1997

Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules

The Journal of Experimental Medicine
J KirbergH von Boehmer

Abstract

In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exported from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intrinsic property or requires continuous survival signals, i.e., engagement of the TCR by major histocompatibility complex (MHC) molecules in the periphery, perhaps in a similar way as occurring during thymic positive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2b mice expressing a transgenic TCR restricted by I-Ed class II MHC molecules. After engraftment with Rag-/- H-2d fetal thymi, CD4+8- peripheral T cells emerged. These cells were isolated and transferred into immunodeficient hosts of H-2b or H-2d haplotype, some of the latter being common cytokine receptor gamma chain deficient to exclude rejection of H-2b donor cells by host natural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells are short lived and disappear within 7 wk, indicating that continuous contact of the TCR with selecting MHC molecules is required for survival of...Continue Reading

Mentioned in this Paper

Interleukin 2 Receptor Gamma
I-E(d) antigen
RAG1 gene
T-Lymphocyte
H2-Bl
Structure of Germinal Center of Lymph Node
Immunologic Deficiency Syndromes
Mice, Inbred BALB C
Graft Acceptance
Neoplasm of Uncertain or Unknown Behavior of Thymus

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