International Immunology Advance Access originally published online on June 1, 2006
International Immunology 2006 18(8):1243-1251; doi:10.1093/intimm/dxl055
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Human V
2V
2 T cells contain cytoplasmic RANTES
1 Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Room N546, Baltimore, MD 21201, USA
2 Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 West Lombard Street, Room N546, Baltimore, MD 21201, USA
3 Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA
4 Present address: Sanofi Pasteur, Swiftwater, PA 18370, USA
Correspondence to: C. D. Pauza; E-mail: pauza{at}umbi.umd.edu
The adult human V
2V
2 T cell repertoire is a product of chronic selection in the periphery. Endogenous antigens drive the expansion of cells expressing the V2V2 TCR. Thus, we would expect the majority of circulating V2V2 T cells to be antigen experienced and to have memory phenotype, in contrast to the alpha/beta TCR+ subsets that include a substantial fraction of naive cells. We sought to characterize functional aspects of V2V2 T cells that might show whether circulating cells are memory or naive. For these studies, we focus on the expression of the CC chemokine regulated upon activation normal T cell expressed and secreted (RANTES). In naive 
ß T cells, an initial stimulus triggers the onset of RANTES transcription followed later by protein expression. In memory CD8+ ß T cells, RANTES mRNA is already present in unstimulated cells and protein expression is triggered immediately by TCR signaling; some cells may also contain RANTES protein in cytoplasmic stores. We show here that the vast majority of circulating human T cells contain RANTES protein in cytoplasmic stores and the chemokine is secreted rapidly after TCR signaling. Primary V2V2 T cell lines obtained after in vitro stimulation with phosphoantigens behaved similarly to circulating V2V2 T cells and contained both RANTES mRNA and protein, but only very low levels of mRNA or protein for macrophage inflammatory protein (MIP)-1 or MIP-1ß. The presence of stored RANTES shows that circulating V2V2 T cells are mostly memory phenotype and capable of rapid chemokine responses to phosphoantigen stimulation. Considering that one of 40 circulating CD3+ lymphocytes is V2V2+, they comprise the largest circulating memory population against a single antigen, and phosphoantigen stimulation will trigger a rapid activation with immediate release of RANTES.
Keywords: chemokines, gamma/delta T cells, human, innate immunity, T cell memory, T cell receptors
Transmitting editor: K. Okumura
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