Publication Date:
1999-05-15
Description:
Misselected CD8 cells that express T cell receptors (TCRs) that do not recognize class I major histocompatibility complex (MHC) protein can emerge from thymic selection. A postthymic quality control mechanism that purges these cells from the repertoire is defined here. The failure of mature CD8 cells to simultaneously engage their TCR and CD8 coreceptor triggers an activation process that begins with inhibition of CD8 gene expression through remethylation and concludes with up-regulation of surface Fas and Fas ligand and cellular apoptosis. Thus, inhibition of a death signal through continued TCR-CD8 coengagement of MHC molecules is a key checkpoint for the continued survival of correctly selected T cells. Molecular defects that prevent delivery of the death signal to mistakenly selected T cells underlie the expansion of double-negative T cells, which is the cellular signature of a subset of systemic autoimmune diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pestano, G A -- Zhou, Y -- Trimble, L A -- Daley, J -- Weber, G F -- Cantor, H -- AI 13600/AI/NIAID NIH HHS/ -- AI 37833/AI/NIAID NIH HHS/ -- CA76176/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 May 14;284(5417):1187-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10325233" target="_blank"〉PubMed〈/a〉
Keywords:
Adoptive Transfer
;
Animals
;
Antigens, CD8/*genetics
;
Antigens, CD95/genetics
;
*Apoptosis
;
CD8-Positive T-Lymphocytes/*cytology/*immunology
;
*DNA Methylation
;
Fas Ligand Protein
;
Gene Expression Regulation
;
Granzymes
;
Histocompatibility Antigens Class I/immunology
;
Kruppel-Like Transcription Factors
;
Lymphocyte Count
;
Membrane Glycoproteins/genetics
;
Mice
;
Mice, Inbred C57BL
;
Receptors, Antigen, T-Cell/genetics/immunology
;
Serine Endopeptidases/genetics
;
Thymus Gland/immunology
;
Trans-Activators/genetics
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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