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. |