Chemokine receptor expression identifies Pre-T helper (Th)1, Pre-Th2, and nonpolarized cells among human CD4+ central memory T cells

The Journal of Experimental Medicine
Laura RivinoJens Geginat

Abstract

We previously reported that central-memory T cells (T(CM) cells), which express lymph node homing receptors CCR7 and CD62L, are largely devoid of effector functions but acquire characteristics of effector-memory T cells (T(EM) cells) (i.e., CCR7(-) T helper [Th]1 or Th2 cells) after stimulation with T cell receptor agonists or homeostatic cytokines. Here we show that three chemokine receptors identify functional subsets within the human CD4(+) T(CM) cell pool. T(CM) cells expressing CXCR3 secreted low amounts of interferon gamma, whereas CCR4(+) T(CM) cells produced some interleukin (IL)-4, but not IL-5. In response to IL-7 and IL-15, CXCR3(+) T(CM) and CCR4(+) T(CM) cells invariably generated fully differentiated CCR7(-) Th1 and Th2 cells, respectively, suggesting that they represent pre-Th1 and pre-Th2 cells. Conversely, CXCR5(+) T(CM) cells lacking CXCR3 and CCR4 remained nonpolarized and retained CCR7 and CD62L expression upon cytokine-driven expansion. Unlike naive cells, all memory subsets had a low T cell receptor rearrangement excision circle content, spontaneously incorporated bromodeoxyuridine ex vivo, and contained cells specific for tetanus toxoid. Conversely, recall responses to cytomegalovirus and vaccinia virus w...Continue Reading

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Methods Mentioned

BETA
acetylation
FCS
Assay
ELISA
flow cytometry
PCR

Software Mentioned

CELLQuest
Softmax

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