Peripheral immature CD2-/low T cell development from type 2 to type 1 cytokine production.
Immature myeloid and NK cells exist, and undergo cytokine-induced differentiation, in the periphery. In this study, we show that also immature CD2(-/low) T cells exist in peripheral blood. These cells produce the type 2 cytokines IL-13, IL-4, and IL-5, but not IFN-gamma or IL-10, and, upon culture with IL-12- and TCR-mediated stimuli, differentiate to IL-13(+)IFN-gamma(+) cells producing high IL-2 levels, and finally IL-13(-)IFN-gamma(+) cells. The monokine combination IL-12, IL-18, and IFN-alpha substitutes for TCR-mediated stimulation to induce the same differentiation process in both immature CD2(-/low) and primary mature CD2(+) IL-13(+) T cells. IFN-alpha is needed to maintain high level IL-2 production, which is confined to type 2 cytokine-producing cells and lost in the IFN-gamma(+) ones. Upon TCR-mediated stimulation, IFN-gamma(+) cells are then induced to produce IL-10 as they undergo apoptosis. These data indicate that peripheral type 2 cytokine(+) T cells are immature cells that can differentiate to effector IFN-gamma(+) cells following a linear monokine-regulated pathway identical with that previously described for NK cells. They define the cellular bases to support that cell-mediated immune responses are regulated not only via Ag-induced activation of mature effector cells, but also via bystander monokine-induced maturation of immature T cells.
Loza
Matthew J
MJ
Kimmel Cancer Center, Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, PA 19107, USA.
Perussia
Bice
B
D000328:Adult; D018801:CD2 Antigens / Q000096:biosynthesis / Q000097:blood; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D015846:Monokines / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D018801:CD2 Antigens; D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D015846:Monokines; D007371:Interferon-gamma