Premium
Variegation of CD4 + T cell phenotypes is regulated by IL‐12 and IFNα
Author(s) -
Davis Ann M,
Ramos Hilario,
Matthews Loderick A.,
Farrar J. David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.846.5
Subject(s) - cxcr3 , effector , phenotype , biology , microbiology and biotechnology , c c chemokine receptor type 7 , t cell , interleukin 4 , immune system , immunology , chemokine , genetics , gene , chemokine receptor
Innate cytokines secreted by antigen presenting cells shape adaptive immune responses to pathogens. For example, viral infections promote robust production of both IL‐12 and IFNα/β, two cytokines which can regulate CD4 + T helper (Th) cell differentiation and effector function. We have demonstrated that IL‐12 is exclusively responsible for directing Th1 development and effector functions in human CD4 + T cells. In contrast to previous reports, IFNα alone was insufficient to promote Th1 development due to inability to maintain stable T‐bet expression. Furthermore, IFNα neither enhanced nor repressed IL‐12‐induced Th1 development. However, IFNα greatly enhanced IL‐12‐induced IL‐2 secretion in human Th cells. Furthermore, while IL‐12 promoted elevated expression of CXCR3, IFNα enhanced expression of CCR7. In cells activated in the presence of both IL‐12 and IFNα, a phenotypic variegation was observed in which IL‐2‐producing cells possessed a CXCR3 lo CCR7 hi phenotype, while IFNγ‐producing cells were CXCR3 hi CCR7 lo . These phenotypic characteristics correlated with function, such that cells sorted for IL‐2 expression possessed greater capacity and phenotypic plasticity than cells sorted for IFNγ xpression. These results suggest a novel role for IFNα/β in the differentiation of Th cells to effector and memory phenotypes. Supported by grants NIH/NIAID AI056222 and NIH/GM GM00820317.