Accumulation of type 2 cytokine+ T cells: differentiation-independent proliferation of pre-existing type 2 T cells.

Analysis of proliferation and cytokine production at the single-cell level indicated that proliferation of pre-existing type 2 cytokine(+) human peripheral naive T cells (CD4(+) and CD8(+)) accounts for the accumulation of type 2 T cells in lymphocytes cultured with IL-2, with or without IL-4, and independently from TCR-mediated stimulation. This is because: firstly,the number of cells progenitor to the type 2 cytokine(+) T cells accumulated in culture is lower than that of the original cytokine(+) cells; secondly, percentages and numbers of the accumulated type 2 cytokine(+) T cells depend on those in the original lymphocyte population; thirdly, no accumulation occurs in cultures of lymphocytes experimentally depleted of type 2 cells; and fourthly, naive T cells do not require proliferation before producing type 2 cytokines. In contrast, accumulation of IFN-gamma(+) T cells in cultures with IL-12 can not be explained with induced proliferation of pre-existing IFN-gamma(+) cells, but depends on differentiation from more-immature cells. These novel insights into the regulation of type 2 and type 1 cytokine(+) T cells provide a new understanding of the cellular bases for the regulation of immune responses and for manipulating the immune system in clinical settings.