title: Higher proportions of circulating FOXP3+ and CTLA-4+ regulatory T cells are associated with lower fractions of memory CD4+ T cells in infants.
abstract: In adults, a majority of FOXP3(+) T(regs) expresses CTLA-4, and this costimulatory molecule is essential to control the expansion of other T cells. However, it remains to be investigated whether FOXP3(+) and/or CTLA-4(+) T(regs) are associated with the expression of memory markers and homing receptors on CD4(+) T cells. Thus, in a prospective newborn-infant cohort study, we examined the proportions of FOXP3(+) and CTLA-4(+) T(regs) within the CD4(+)CD25(+) T cell population and the fractions of CD4(+) T cells that expressed CD45RA, CD45RO, HLA-DR, α(4)β(7), CD62L, and CCR4 at several time-points during the first 3 years of life using flow cytometry. With the use of multivariate factor analysis, we found that a high proportion of FOXP3(+) or CTLA-4(+) T(regs) during the first 18 months of life was associated positively with the fraction of T cells that expressed a naïve phenotype (CD45RA and α(4)β(7)) and inversely related to the fraction of T cells that expressed a memory phenotype (CD45RO and CCR4) later in childhood. In conclusion, FOXP3(+) or CTLA-4(+) T(regs) may modulate CD4(+) T cell activation and homing receptor expression in children.
authors.affiliation: Departments of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hardis
authors.initials: H
authors.lastname: Rabe
authors.forename: Anna-Carin
authors.initials: AC
authors.lastname: Lundell
authors.forename: Kerstin
authors.initials: K
authors.lastname: Andersson
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Adlerberth
authors.forename: Agnes E
authors.initials: AE
authors.lastname: Wold
authors.forename: Anna
authors.initials: A
authors.lastname: Rudin
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000096:biosynthesis* / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000097:blood*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016201:Receptors, Lymphocyte Homing / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016201:Receptors, Lymphocyte Homing