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

Inna V. Grishkan, Achilles Ntranos, Peter A. Calabresi, Anne R. Gocke

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalCellular Immunology
Volume284
Issue number1-2
DOIs
StatePublished - Jul 2013

Keywords

  • CD4 co-receptor
  • Double-negative T cells
  • Helper T cells
  • Kv1.3

ASJC Scopus subject areas

  • Immunology

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