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Scand J Immunol ; 77(2): 125-34, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23126599

RESUMO

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-ß1 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-ß1. TGF-ß1 and IL-2 were both required for optimal expression of CD103. In addition, TGF-ß1 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-ß1 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.


Assuntos
Interleucina-2/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos CD4/genética , Antígenos CD4/metabolismo , Antígenos CD8/genética , Antígenos CD8/metabolismo , Células Cultivadas , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunofenotipagem , Cadeias alfa de Integrinas/genética , Cadeias alfa de Integrinas/metabolismo , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Linfócitos T Reguladores/citologia
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