Cutting edge: a T-bet-independent role for IFN-alpha/beta in regulating IL-2 secretion in human CD4+ central memory T cells.
IL-2 is a hallmark cytokine secreted by central memory CD4(+) T cells (T(CM)). Although naive cells rapidly secrete IL-2 in response to Ag stimulation, IL-12 inhibits IL-2 secretion in daughter cells as they differentiate into Th1 cells. In this study, we uncover a unique role for IFN-alpha in regulating IL-2 secretion by human T(CM) cells. IFN-alpha synergized with IL-12 to enhance a subset of cells that secreted high and sustained levels of IL-2. These IL-2-secreting cells displayed phenotypic and functional characteristics of T(CM) and were capable of generating IFN-gamma-secreting effectors upon secondary activation. T-bet has been implicated in negatively regulating IL-2 secretion in murine T cells; however, T-bet expression did not inhibit IFN-alpha-dependent IL-2 secretion in human T(CM) cells. Thus, our results highlight a unique role for IFN-alpha in regulating the development of IL-2-secreting human T(CM) cells.
Davis
Ann M
AM
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ramos
Hilario J
HJ
Davis
Laurie S
LS
Farrar
J David
JD
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
D016898:Interferon-alpha; D007376:Interleukin-2; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; D018664:Interleukin-12; D016899:Interferon-beta