Interleukin 2 (IL-2) and interleukin 7 (IL-7) reciprocally induce IL-7 and IL-2 receptors on γδ T-cell receptor-positive intraepithelial lymphocytes

Abstract

In this study, we describe the interaction between cytokine and cytokine receptor (R) for the activation and proliferation of γδ T-cell receptor. positive T cells (γδ T cells). γδ T cells isolated from murine intestinal intraepithelial lymphocytes (IELs) were separated into γδ(Dim) and γδ(Bright) fractions according to the intensity of γδ T-cell receptor expression. The γδ(Dim) T cells express low levels of IL-2R and IL-7R as shown by flow cytometry and reverse transcriptase-PCR analysis, whereas γδ(Bright) T cells did not express either receptor. Our study also revealed that recombinant murine (rm)IL-2 and rmIL-7 reciprocally induced high expressions of IL-7R and IL-2R, respectively, on γδ(Dim) T cells but not on γδ(Bright) IELs. Thus, treatment of γδ(Dim) T cells with rmIL-2 and rmIL- 7 resulted in high proliferative responses, whereas γδ(Bright) T cells did not respond to these two cytokines. The sources of these two cytokines for γδ(Dim) T cells were neighboring epithelial cells (IL-7) and αβ IELs (IL- 2 and IL-7). Cytokine signaling by IL-2 and IL-7 from αβ T cells and epithelial cells was necessary for the expression of IL-7R and IL-2R, respectively, on a subset of γδ T cells (e.g., γδ(Dim) T cells) in mucosa-associated tissue for subsequent activation and cell division.