Interleukin (IL)-13 is a cytokine originally identified as a product of activated T cells. Little is known, however, about IL-13 production by human T cells and its modulation by other cytokines. Here, we show that IL-13 is produced by activated human CD4(+) and CD8(+) CD45R0(+) memory T cells and CD4(+) and CD8(+) CD45RA(+) naive T cells. In contrast, IL-4, which shares many biological activities with IL-13, is only produced by CD45R0(+) T cells following activation. Analysis of intracellular cytokine production by single CD45RA(+) and CD45R0(+) T cells indicated that IL-13 continued to be produced for more than 24 h after stimulation, whereas IL-4 could not be detected after 24 h. These data were confirmed by measurement of specific mRNA and suggest that IL-13, unlike IL-4, but like interferon-gamma (IFN-gamma), is a cytokine with long-lasting kinetics. The majority of human CD45R0(+) T cells produced IL-4 and IL-13 simultaneously. In contrast, IFN-gamma protein was generally not co-expressed with IL-4 or IL-13. IL-4 added to primary cultures of highly purified peripheral blood T cells activated by the combination of anti-CD3+anti-CD28 mAb enhanced IL-13 production by CD45RA(+) and to a lesser extent by CD45R0(+) T cells. Under these conditions, however, IL-12 inhibited IL-13 production by CD45RA(+) T cells and to a lesser extend by CD45R0(+) T cells in a dose-dependent fashion. These inhibiting effects were not related to enhanced IFN-gamma production induced by IL-12, since IFN-gamma by itself did not affect IL-13 production. Collectively, our data indicate that IL-13 is produced by peripheral blood T cells which also produce IL-4, but not IFN-gamma, and by naive CD45RA(+) T cells which, in contrast, fail to produce IL-4. These observations, together with the long-lasting production of IL-13, suggest that IL-13 may have IL-4-like functions in situations where T cell-derived IL-4 is still absent or where its production has already been down-regulated.
