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Peripheral Immature CD2^-/low T Cell Development from Type 2 to Type 1 Cytokine Production¹

Kimmel Cancer Center, Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, PA 19107

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- or IL-10, and, upon culture with IL-12- and TCR-mediated stimuli, differentiate to IL-13⁺IFN-⁺ cells producing high IL-2 levels, and finally IL-13^-IFN-⁺ cells. The monokine combination IL-12, IL-18, and IFN- 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- is needed to maintain high level IL-2 production, which is confined to type 2 cytokine-producing cells and lost in the IFN-⁺ ones. Upon TCR-mediated stimulation, IFN-⁺ 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-⁺ 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.

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