Journal
IMMUNOLOGY LETTERS
Volume 98, Issue 1, Pages 23-31Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2004.10.022
Keywords
lymphopenia; autoimmunity; T cell homeostasis lymphopenia-induced proliferation; costimulation; regulatory CD25(+)CD4 T cells
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Funding
- NIDDK NIH HHS [R01 DK061961] Funding Source: Medline
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It is well recognized that the composition of the mature T cell population is subject to strict homeostatic control. The TCR repertoire and relative proportions of various T cell subsets are established in the thymus, and continue to be shaped and regulated in the periphery. As the thymic function declines, peripheral homeostatic mechanisms assume increasing importance. Indeed, loss of thymic function does not lead to progressive decline of T cell numbers because peripheral mechanisms ensure that the size of the T cell population is maintained due to proliferation of residual cells. However, our current understanding of the basic mechanisms of 'homeostatic' or lymphopenia-induced proliferation suggests that this drive to maintain population size may be accompanied by loss of TCR diversity and emergence of auto-reactive effector T cells. This prediction is Supported by experimental and clinical evidence. This consideration is important because lymphopenia is seen commonly in clinical practice as a consequence of viral infections, or medical treatment of cancer, autoimmunity, and graft rejection. Lymphopenia may be a simple link between viral infections and autoimmunity, and may be one reason for common failure of very potent, but non-specific, immunosuppressive drugs in current clinical use. (c) 2004 Elsevier B.V. All rights reserved.
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