title: A new subset of human naive CD8+ T cells defined by low expression of IL-7R alpha.
abstract: Concomitant with an increased number of memory-type cells, the amount of naive T cells steadily declines with age. Although the regulatory mechanisms behind this conversion are not fully understood, the suggestion is that both alterations in thymic output and homeostatic signals mold the naive T cell pool. In this study, we identify a new subset of circulating CD27(high)CD45RA(high) CD8+ T cells characterized by low IL-7Ralpha message and protein expression. Analysis of TCR repertoire and TCR excision circle content together with ex vivo recovery of IL-7Ralpha expression indicated that these cells should be placed into the naive T cell pool. Compared with conventional IL-7Ralpha(high) naive T cells, this subset displayed significantly lower levels of CD28 and higher levels of HLA-DR. Proliferative responses to anti-CD3/CD28 mAbs were indistinguishable from conventional naive T cells, but the responsiveness to IL-7 was limited. Strikingly, IL-7Ralpha(low) naive T cells were particularly increased in circumstances of naive CD8+ T cells shortage, as in the elderly, in patients early after hemopoietic stem cell transplantation, and in HIV-infected individuals. As common gamma chain cytokines induce rapid down-regulation of IL-7Ralpha, we propose that this new subset of naive T cells may encompass cells that have recently received homeostatic signals.
authors.affiliation: Department of Experimental Immunology, Laboratory for Experimental Immunology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Alves
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.forename: Kiki
authors.initials: K
authors.lastname: Tesselaar
authors.forename: Eddy
authors.initials: E
authors.lastname: Roosnek
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
chemical_list: D020395:Receptors, Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C415350:interleukin-7 receptor, alpha chain; D017493:Leukocyte Common Antigens