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Splenic NK1.1-Negative, TCRß Intermediate CD4⁺ T Cells Exist in Naive NK1.1 Allelic Positive and Negative Mice, with the Capacity to Rapidly Secrete Large Amounts of IL-4 and IFN- Upon Primary TCR Stimulation¹

Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030

Splenic NK1.1⁺CD4⁺ T cells that express intermediate levels of TCRß molecules (TCR^int) and the DX5 Ag (believed to identify an equivalent population in NK1.1 allelic negative mice) possess the ability to rapidly produce high quantities of immunomodulatory cytokines, notably IL-4 and IFN-, upon primary TCR activation in vivo. Indeed, only T cells expressing the NK1.1 Ag appear to be capable of this function. In this study, we demonstrate that splenic NK1.1-negative TCR^intCD4⁺ T cells, identified on the basis of FcR expression, exist in naive NK1.1 allelic positive (C57BL/6) and negative (C3H/HeN) mice with the capacity to produce large amounts of IL-4 and IFN- after only 8 h of primary CD3 stimulation in vitro. Furthermore, a comparison of the amounts of early cytokines produced by FcR⁺CD4⁺TCR^int T cells with NK1.1⁺CD4⁺ or DX5⁺CD4⁺TCR^int T cells, simultaneously isolated from C57BL/6 or C3H/HeN mice, revealed strain and population differences. Thus, FcR defines another subpopulation of splenic CD4⁺TCR^int cells that can rapidly produce large concentrations of immunomodulatory cytokines, suggesting that CD4⁺TCR^int T cells themselves may represent a unique family of immunoregulatory CD4⁺ T cells whose members include FcR⁺CD4⁺ and NK1.1/DX5⁺CD4⁺ T cells.

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