Gammadelta T lymphocyte homeostasis is negatively regulated by beta2-microglobulin.
Gammadelta T lymphocyte homeostasis is negatively regulated by beta2-microglobulin.
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DOI：
10.4049/jimmunol.0803165
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发表时间：
2009-02-15
期刊：
影响因子：
--
通讯作者：
O'Brien RL
中科院分区：
文献类型：
--
作者：
French JD;Roark CL;Born WK;O'Brien RL
Successful application of γδ T cells in adoptive cell therapies depends upon our ability to maintain these cells in vivo. Using an adoptive transfer model to study lymphopenia-induced homeostatic expansion, we show that CD8+ and NK1.1+ γδ T cell subsets are differentially regulated. While CD8+ γδ T cells have an early and sustained advantage following transfer into TCRβ−/−/δ−/− mice, NK1.1+ γδ T cells proliferate slowly and are maintained at low numbers. The advantage of the CD8+ subset could not be explained by increased bcl-2 or cytokine receptor expression but did correlate with Vγ4+ and Vδ5+ expression. Despite the role of CD8 in MHCI recognition by αβ T cells, β2m-associated MHCI molecules were not required for CD8+ γδ T cell homeostatic expansion. Surprisingly, all γδ T cells, including the CD8+ subset, exhibited enhanced proliferation following adoptive transfer into Rag1−/−/β2m−/− compared to Rag1−/− recipients. This effect was most notable for the NK1.1+ subset, which expresses high levels of NKG2A/CD94 and Ly49. Although expression of these inhibitory receptors correlated with poor homeostatic expansion in the presence of β2m, γδ T cell homeostatic proliferation in TCRβ−/−/δ−/− mice was not altered in the presence of Ly49C/I and NKG2 blocking antibodies. While the mechanism by which β2m negatively regulates γδ T cell homeostasis remains to be determined, this observation is unique to γδ T cells and confirms that multiple mechanisms are in place to maintain strict regulation of both the size and the composition of the γδ T cell pool.
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