CD31, a Valuable Marker to Identify Early and Late Stages of T Cell Differentiation in the Human Thymus.
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+CD8α+β-). After β-selection, CD31 expression levels become low to undetectable. CD31 expression then increases and peaks on CD3highCD4+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-mature CD4+thymocytes. CD31 expression on TCRγδ 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-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: β-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.
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Marc
M
Douaisi
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Rachel S
RS
Resop
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Maho
M
Nagasawa
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
Joshua
J
Craft
Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095.|University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA 90024.|University of California Los Angeles AIDS Institute and Center for AIDS Research, Los Angeles, CA 90095; and.
Beth D
BD
Jamieson
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Bianca
0000-0002-8401-5319
B
Blom
Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095; uittenbo@ucla.edu.|University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA 90024.|University of California Los Angeles AIDS Institute and Center for AIDS Research, Los Angeles, CA 90095; and.|Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095.
Christel H
CH
Uittenbogaart
D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017637:Clonal Deletion; D060966:Clonal Selection, Antigen-Mediated; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*
D018952:Antigens, CD34; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011948:Receptors, Antigen, T-Cell