Single IL-2-secreting precursor CD4 T cell can develop into either Th1 or Th2 cytokine secretion phenotype.
Immunocompetent T lymphocytes in peripheral tissues mainly secrete IL-2 when first stimulated, whereas effector T lymphocytes generated during an immune response secrete different cytokine patterns, such as the Th1, Th2, or other phenotypes displayed by in vitro T cell clones. In this paper, we have examined whether the cell populations that have distinctive cytokine-producing capabilities represent different cell lineages or whether they are derived from the same uncommitted precursor T cell. During allostimulation of CD4+ spleen T cells, TGF-beta inhibited the development of T cells that could produce the Th2 cytokines IL-4 and IL-5. Anti-IFN-gamma inhibited the development of Th1-like IFN-gamma-secreting cells, and the combination of TGF-beta and anti-IFN-gamma resulted in the proliferation of a cell population that produced IL-2, but not IFN-gamma, IL-4, or IL-5, on restimulation. These IL-2-producing T cells expressed low levels of CD45RB and MEL14 and high levels of CD44. Clones of IL-2-producing T cells were isolated, and either bulk culture or clonal IL-2-producing populations acquired the ability to secrete Th1 or Th2 cytokine patterns when restimulated in the presence of TGF-beta or IL-4, respectively. These results demonstrate that both Th1- and Th2-like cells can be derived from a bipotential IL-2-producing precursor CD4+ T cell.
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Department of Immunology, University of Alberta, Edmonton, Canada.
Mosmann
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016207:Cytokines; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma