4.7 Article

T cell regulation as a side effect of homeostasis and competition

期刊

JOURNAL OF EXPERIMENTAL MEDICINE
卷 197, 期 4, 页码 451-460

出版社

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021387

关键词

T cell regulation; homeostasis; lymphopenia; immune pathology; CD4T cells

资金

  1. Wellcome Trust Funding Source: Medline

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We have previously hypothesized that maintaining a balanced peripheral immune system may not be the sole responsibility of a specialized subset of T cells dedicated to immune regulation, but also a side effect of normal competition for shared resources within an intact immune system. Here we show that regulatory activity is correlated with high homeostatic expansion potential, reflecting the avidity for self-peptide:MHC complexes. Monoclonal transgenic T cells with high homeostatic expansion potential and lacking characteristics previously associated with regulatory function were able to regulate wasting disease induced by transfer of a small number of naive CD45RB(hi) CD4 T cells into lymphopenic hosts. Self-regulatory function is also found in the naive polyclonal T cell repertoire depleted of CD25(+) T cells. T cells capable of preventing immune pathology, like the transgenic T cells, express higher than average levels of CD5, an indicator of avidity for self:MHC peptide complexes. We therefore propose that dysregulated expansion of potentially pathogenic T cells in a lymphopenic environment can be prevented by members of the naive T cell repertoire, irrespective of their specificity, as a side effect of their response to homeostatic and antigenic stimulation.

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