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IL‐12 and IFNα/β regulate non‐redundant functions in human CD8+ T cells
Author(s) -
Ramos Hilario J,
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.1070.21
Subject(s) - perforin , cytotoxic t cell , granzyme , granzyme b , microbiology and biotechnology , biology , cxcr3 , cd8 , interleukin 21 , immunology , cytokine , t cell , c c chemokine receptor type 7 , chemokine , immune system , chemokine receptor , in vitro , biochemistry
During viral infection, dendritic cells secrete the innate cytokines IL‐12 and IFNα/β to facilitate viral clearance. These cytokines have been linked to CD8 + T cell and are widely thought to act in a redundant manner to facilitate cytokine secretion and cytolytic activity. We examined the ability of IL‐12 and IFNα/β to drive these responses in human CD8 + CD45RA + T cells. We found that IL‐12 was sufficient for the generation of CD8 + effector cell activity, marked by IFNγ and TNFα secretion and strong cytolytic activity. In contrast, IFNα/β alone did not promote IFNγ or TNFα. Although, IFNα/β markedly induced perforin and granzyme B expression as a whole, these cells displayed functionally defective lytic activity in the absence of IL‐12 signaling. Thus, IL‐12 but not IFNα/β regulates primary effector functions in human CD8 + T cells. Interestingly, IFNα/β enhanced the expression of lymph node homing receptor CCR7 on a subset of T cells. This subpopulation displayed various characteristics of a memory phenotype, such as low CXCR3 and perforin expression while retaining granzyme B expression. Further, development of this CCR7 hi sub population was regulated solely by IFNα/β and was independent of the effects of IL‐12. These results demonstrate that IL‐12 and IFNα/β are not functionally redundant and in fact, impart unique phenotypes on human CD8 + T cells. This study is supported by a grant from the National Institutes of Health/National Institute of Allergy and Infectious Disease (AI56222) and by a predoctoral fellowship from the National Instititue of Health/Nation Institute of Allergy and Infectious Disease (AI68622).