title: Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA-CD27- T cell subset contains specialized primed T cells.
abstract: CD27, a member of the TNFR family, is expressed on most but not all peripheral blood CD4+ T cells. The small fraction of CD4+ T cells with a CD27- phenotype exclusively reside within the CD45RA-CD45RO+ subset. We previously provided evidence that CD27- cells are functionally differentiated cells that have lost CD27 expression as a result of persistent antigenic stimulation. We here show that compared with CD4+CD45RA-CD27+ cells, CD4+CD45RA-CD27- lymphocytes have a high expression of the beta 1 integrins VLA-4 and -5 and of the beta 2 integrin CD11b. Molecules implicated in homing of T cells to peripheral lymphnodes like CD31 and CD62L (L-selectin) are poorly expressed on CD27- cells, whereas receptors involved in organ-specific homing, e.g., cutaneous lymphocyte Ag and HML-1 (alpha E beta 7), are present on CD27- rather than CD27+ T lymphocytes. CD27+ and CD27- cells do not differ notably in the expression of activation molecules such as CD25, CD38, and CD70 (CD27 ligand) but CD7 is markedly absent on approximately half of the CD27- cells. Analysis of mutations in the HPRT gene, as measurement for the amount of cell divisions that have occurred in particular T cell populations in vivo, showed that CD45R0+ cells have a 2 to 5 times higher mutant frequency than CD45RA+ cells, whereas CD45R0+CD27- cells do not differ in this respect from CD45R0+CD27+ cells. In line with this latter finding, cells in G2M phase can only be found in the transitional, CD45RAbrightCD45R0bright subset but not in CD45R0+, CD45RA-, or CD27- cells. Our results imply that the CD27- population contains tissue-specific, specialized "primed" T cells that evolve in vivo independently from extensive cellular division.
authors.affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: P A
authors.initials: PA
authors.lastname: Baars
authors.forename: M M
authors.initials: MM
authors.lastname: Maurice
authors.forename: M
authors.initials: M
authors.lastname: Rep
authors.forename: B
authors.initials: B
authors.lastname: Hooibrink
authors.forename: R A
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells / Q000276:immunology; D004252:DNA Mutational Analysis; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016023:Integrins / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D016176:T-Lymphocyte Subsets; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016023:Integrins; D018124:Receptors, Tumor Necrosis Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens