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Publication : Helper T cells down-regulate CD4 expression upon chronic stimulation giving rise to double-negative T cells.

First Author  Grishkan IV Year  2013
Journal  Cell Immunol Volume  284
Issue  1-2 Pages  68-74
PubMed ID  23933188 Mgi Jnum  J:202348
Mgi Id  MGI:5518512 Doi  10.1016/j.cellimm.2013.06.011
Citation  Grishkan IV, et al. (2013) Helper T cells down-regulate CD4 expression upon chronic stimulation giving rise to double-negative T cells. Cell Immunol 284(1-2):68-74
abstractText  Double-negative T (DNT) cells are alphabetaTCR(+)CD3(+)CD4(-)CD8(-)NK1.1(-) cells that constitute a small but significant proportion of the alphabetaTCR(+) T cells. Their developmental pathway and pathological significance remain unclear. In the present study, we utilized chronic in vitro stimulation of CD4(+) T cells to mimic immune hyper-activation of autoimmune lymphoproliferative syndrome and systemic lupus erythematosus, conditions characterized by DNT cells accumulation. After approximately 4-5 rounds of stimulation, the CD3(+)CD4(-) population became apparent. These cells did not express CD8, NK1.1, gammadeltaTCR, or B220, exhibited a highly proliferative effector phenotype, and were dependent on T cell receptor (TCR) stimulation for survival. Moreover, CD3(+)CD4(-) cells expressed MHC class II-restricted alphabetaTCR, indicative of their origin from a CD4(+) T cell population. The results presented herein illustrate a novel method of DNT cell generation in vitro and suggest that immune hyper-activation could also be implicated in the genesis of the disease-associated DNT cells in vivo.
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