title: The ex vivo induction of human CD103⁺ CD25hi Foxp3⁺ CD4⁺ and CD8⁺ Tregs is IL-2 and TGF-β1 dependent.
abstract: The expression of the integrin αE (CD103), may enhance the retention of regulatory T cells to peripheral inflammatory sites and possibly contribute to their suppressive potential. The aim of this study was to define the regulatory role of IL-2 and TGF-β1 on the CD103 expression and the optimal in vitro conditions for the induction/expansion of human CD4(+) and CD8(+) Tregs. Cord blood mononuclear cells (CBMC) were stimulated under various culture conditions, including anti-CD3, anti-CD28, IL-2 and TGF-β1. TGF-β1 and IL-2 were both required for optimal expression of CD103. In addition, TGF-β1 and IL-2 synergistically induced CD103 expression on CD8(+) T cells, whereas, only additive induced expression was noted on CD4(+) T cells. Surprisingly, CD103 expression was not dependent upon CD28 costimulation. IL-2 also played a central role in CD103 expression by CD25(hi) Foxp3+ Tregs. IL-2, TGF-β1 and anti-CD3 defined the optimal stimulatory conditions favouring the induction/expansion of both CD4(+) and CD8(+) human Tregs from naive CBMC. Thus, this study provides new insights into the regulatory role of IL-2 upon CD103 expression by human cord blood CD4(+) and CD8(+) T cells. Furthermore, it identifies the in vitro culture conditions driving the differentiation of the novel phenotype CD4(+) and CD8(+) CD103(+) CD25(hi) Foxp3+ Tregs from human CBMC.
authors.affiliation: Department of Immunology, Landspitali - University Hospital, Reykjavik, Iceland.
authors.forename: B
authors.initials: B
authors.lastname: Gunnlaugsdottir
authors.forename: S M
authors.initials: SM
authors.lastname: Maggadottir
authors.forename: I
authors.initials: I
authors.lastname: Skaftadottir
authors.forename: B R
authors.initials: BR
authors.lastname: Ludviksson
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D039001:Integrin alpha Chains; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C091367:alpha E integrins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II