Single IL-2-secreting precursor CD4 T cell can develop into either Th1 or Th2 cytokine secretion phenotype

Abstract

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.