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The clone size of peripheral CD8 T cells is regulated by TCR promiscuity.

ABSTRACT: Positive selection in the thymus and peripheral T cell survival depend on T cell receptor (TCR)-major histocompatibility complex (MHC) interactions, but it is not yet clear if both events follow exactly the same rules. We studied peripheral T cell survival and clone sizes in conditions of progressive reduction of restricting MHC-bearing cells or progressive ablation of different MHC molecules. Different CD8(+) T cell clones/polyclonal populations showed different survival and/or lymphopenia-driven proliferation requirements. We could correlate clone sizes to the capacity of each TCR to interact with different types of MHC complexes. Thus, although repertoire selection in the thymus is mainly conditioned by the affinity of TCR-MHC interactions, peripheral selection is determined by TCR cross-reactivity to environmental ligands.

SUBMITTER: Hao Y

PROVIDER: S-EPMC2118336 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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The clone size of peripheral CD8 T cells is regulated by TCR promiscuity.

Hao Yi Y Legrand Nicolas N Freitas Antonio A AA

The Journal of experimental medicine 20060612 7

Positive selection in the thymus and peripheral T cell survival depend on T cell receptor (TCR)-major histocompatibility complex (MHC) interactions, but it is not yet clear if both events follow exactly the same rules. We studied peripheral T cell survival and clone sizes in conditions of progressive reduction of restricting MHC-bearing cells or progressive ablation of different MHC molecules. Different CD8(+) T cell clones/polyclonal populations showed different survival and/or lymphopenia-driv ...[more]

PMID: 16769997

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Project description:The role of conventional TCR??+CD4+ or TCR??+CD8?+ single-positive (sp) T lymphocytes in adaptive immunity is well-recognized. However, non-conventional T cells expressing TCR?? or TCR?? but lacking CD4 and CD8? expression [i.e., CD4-CD8?- double-negative (dn) T cells] are thought to play a role at the interface between the innate and adaptive immune system. Dn T cells are frequent in swine, cattle or sheep and predominantly express TCR??. In contrast, TCR??+ T cells are rare in dogs. In this study, we identified a high proportion of canine dn T cells in the TCR??+ T cell population of PBMC, lymphatic and non-lymphatic organs. In PBMC, the frequency of this T cell subpopulation made up one third of the frequency of TCR??+CD4+ sp, and almost half of the frequency of TCR??+CD8?+ sp T cells (i.e., ~15% of all TCR??+ T cells). Among TCR??+CD4-CD8?- dn T cells of PBMC and tissues, FoxP3+ cells were identified indicating regulatory potential of this T cell subset. 80% of peripheral blood FoxP3+TCR??+CD4-CD8?- dn T cells co-expressed CD25, and, interestingly, also the FoxP3-negative TCR??+CD4-CD8?- dn T cells comprised ~34% CD25+ cells. Some of the FoxP3-positive TCR??+CD4-CD8?- dn T cells co-expressed GATA-3 suggesting stable function of regulatory T cells. The frequency of GATA-3 expression by FoxP3-TCR??+CD4-CD8?- dn T cells was even higher as compared with TCR??+CD4+ sp T cells (20.6% vs. 11.9%). Albeit lacking FoxP3 and CD25 expression, TCR??+CD4-CD8?- dn T cells also expressed substantial proportions of GATA-3. In addition, TCR??+CD4-CD8?- dn T cells produced IFN-? and IL-17A upon stimulation. T-bet and granzyme B were only weakly expressed by both dn T cell subsets. In conclusion, this study identifies two dn T cell subsets in the dog: (i) a large (~7.5% in Peyer's patches, ~15% in lung) population of TCR??+CD4-CD8?- dn T cells with subpopulations thereof showing an activated phenotype, high expression of FoxP3 or GATA-3 as well as production of IFN-? or IL-17A and (ii) a small TCR??+CD4-CD8?- dn T cell subset also expressing GATA-3 without production of IFN-? or IL-17A. It will be exciting to unravel the function of each subset during immune homeostasis and diseases of dogs.

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The clone size of peripheral CD8 T cells is regulated by TCR promiscuity.

Publications

The clone size of peripheral CD8 T cells is regulated by TCR promiscuity.

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