Journal
JOURNAL OF IMMUNOLOGY
Volume 198, Issue 6, Pages 2310-2319Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500350
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Funding
- National Institutes of Health Grants [AI102771, AI 080564]
- National Institute on Aging Grant [AG030327]
- Multicenter AIDS Cohort Study National Institutes of Health/National Institute of Allergy and Infectious Diseases [AI035040]
- National Institutes of Health T32 Training Grant [5T32HL086345-08]
- University of California HIV/AIDS Research Program Idea Award [ID08-LA-053]
- University of California Los Angeles Jonsson Comprehensive Cancer Center
- National Institutes of Health Grant [CA-16042, AI-28697]
- Jonsson Comprehensive Cancer Center
- University of California Los Angeles AIDS Institute
- David Geffen School of Medicine, University of California Los Angeles
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Although CD31 expression on human thymocytes has been reported, a detailed analysis of CD31 expression at various stages of T cell development in the human thymus is missing. In this study, we provide a global picture of the evolution of CD31 expression from the CD34(+) hematopoietic precursor to the CD45RA(+) mature CD4(+) and CD8(+) single-positive (SP) T cells. Using nine-color flow cytometry, we show that CD31 is highly expressed on CD34(+) progenitors and stays high until the early double-positive stage (CD3(-)CD4(+) CD8 alpha(+)beta(-)). After beta-selection, CD31 expression levels become low to undetectable. CD31 expression then increases and peaks on CD3(high) CD4(+) CD8(+) double-positive thymocytes. However, following positive selection, CD31 expression differs dramatically between CD4(+) and CD8(+) lineages: homogeneously high on CD8 SP but lower or negative on CD4 SP cells, including a subset of CD45RA(+) CD31 2 mature CD4(+) thymocytes. CD31 expression on TCR gamma delta thymocytes is very similar to that of CD4 SP cells. Remarkably, there is a substantial subset of semimature (CD45RA(-)) CD4 SP thymocytes that lack CD31 expression. Moreover, FOXP3(+) and ICOS+ cells are overrepresented in this CD31 2 subpopulation. Despite this CD31(-) CD45RA(-) subpopulation, most egress-capable mature CD45RA(+) CD4 SP thymocytes express CD31. The variations in CD31 expression appear to coincide with three major selection processes occurring during thymopoiesis: b-selection, positive selection, and negative selection. Considering the ability of CD31 to modulate the TCR's activation threshold via the recruitment of tyrosine phosphatases, our results suggest a significant role for CD31 during T cell development.
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