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

Abstract

Double-negative T (DNT) cells are αβTCR(+)CD3(+)CD4(-)CD8(-)NK1.1(-) cells that constitute a small but significant proportion of the αβTCR(+) 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, γδTCR, 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 αβTCR, 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.

• Authors: Inna V Grishkan, Achilles Ntranos, Peter A Calabresi, Anne R Gocke
• Journal: Cellular immunology (Cell Immunol) 2013 Jul-Aug Vol. 284 Issue 1-2 Pg. 68-74 ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 23933188 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Animals
• Autoimmune Lymphoproliferative Syndrome (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Proliferation
• Down-Regulation
• Female
• Flow Cytometry
• Lupus Erythematosus, Systemic (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Phenotype
• Receptors, Antigen, T-Cell, alpha-beta (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)