Single‐cell analyses of CD4+ T cells from αβ T cell receptor‐transgenic mice: a distinct mucosal cytokine phenotype in the absence of transgene‐specific antigen

Abstract

Development of distinct CD4⁺ T cell cytokine phenotypes may be conditioned by the anatomic site in which activation occurs. A double‐label in situ hybridization technique was used to characterize co‐expression of cytokine mRNA in antigen‐specific responses of Peyer's patch (PP), lamina propria (LP), and splenic (SP) CD4⁺ T cells isolated from αβ T cell receptor‐transgenic mice. Interleukin (IL)‐2 was the dominant cytokine expressed by antigen‐stimulated PP and SP populations, though it was expressed by a minority of the activated T cells. Cells that expressed interferon (IFN)‐γ were less frequent, and IL‐4, IL‐5, and IL‐10 were infrequent. In contrast, cells that expressed IFN‐γ or IL‐10 were most frequent in the LP population, with lower frequencies of IL‐2, and few IL‐4‐ and IL‐5‐positive cells. Co‐expression of two cytokines by the same cell was the exception, regardless of the anatomic site from which the T cells were isolated. The surface phenotype of transgene‐positive T cells isolated from each anatomic site was distinct, despite the absence of in vivo exposure to antigen for which the transgenic T cell receptor is specific. These data suggest that the cytokine responses of CD4⁺ T cells may be conditioned by the microenvironment, independently of specific antigen, and that the LP CD4⁺ T population has a distinct cytokine expression pattern with counter‐regulatory properties that may be important for homeostasis in mucosal immune tissues.