In utero treatment with monoclonal antibody to IL-2 receptor β-chain completely abrogates development of Thy-1⁺ dendritic epidermal cells

Abstract

Interleukin-2 (IL-2), a crucial growth factor for mature T lymphocytes, is produced in fetal thymus under developmental control, although its biological significance remains unclear. We found that the two distinct subunits of the IL-2 receptor, i.e. the alpha-chain (IL-2R alpha) and the beta-chain (IL-2R beta), were expressed in an almost mutually exclusive fashion throughout fetal thymus ontogeny, and that the blockade of IL-2R beta, a signal transducing component of IL-2R, by administering a neutralizing mAb to IL-2R beta resulted in the complete and selective disappearance of Thy-1+ skin dendritic epidermal cells. Development of any other T cell subsets was uncompromised. This indicates that IL-2 plays a crucial role in the development of fetal V gamma 5+ cells and their descendants.

Developmental and Functional Defects of Thymic and Epidermal Vγ3 Cells in IL-15-Deficient and IFN Regulatory Factor-1-Deficient Mice

“…␥␦ T cells derived from the fetal thymus and from adult skin, spleen, or peritoneal cavity can proliferate in vitro in response to IL-2, IL-7, or IL-15 (13)(14)(15)(16)(17)(18)(19). ␥ c Ϫ/Ϫ mice have confirmed these findings, as these mice have defects in ␥␦ T cell development.…”

“…We were not able to measure IL-15 protein levels, as no reliable IL-15 ELISA method is available at the moment. It has already been postulated that skin epithelium has the capacity to induce DETC maturation (40) and that cytokines expressed in the epidermis might determine the localization and maturation of V␥3 ϩ DETCs in the epidermis (8,17,18,43,44 (11), suggest that IRF-1 controls the expression of other, non-IL-15, target gene(s) that contributes to the acquisition of cytotoxicity in V␥3 cells. In this context, IL-12 has been shown to enhance ␥␦ T cell cytotoxicity activity (29,33).…”

“…In IL-7R Ϫ/Ϫ and IL-7 Ϫ/Ϫ mice, maturation of V␥3 cells in the fetal thymus is inhibited and no V␥3 DETCs are detected in the skin, showing the importance of IL-7 in the development and/or survival of V␥3 cells or their precursors (8,21). In addition, several other studies have suggested a role for IL-15 and IL-2 in the development of V␥3 cells (18,22,23). Both cytokines interact with receptor complexes that contain the ␥ c , the IL-2R␤ chain, and a specific IL-2R or IL-15R ␣-chain (22,23).…”

Thymic Stromal‐Cell Abnormalities and Dysregulated T‐Cell Development in IL‐2‐Deficient Mice

“…Among the cytokines that are normally produced within the thymus during T-cell development, has been the most intensively studied. The expression of functional by developing thymocytes (Skinner, et al, 1987;Jenkinson et al, 1987;Waanders et al, 1989Waanders et al, , 1990, and the ability of anti-IL-2R antibodies to disrupt thymocyte growth and/or proliferation in vivo (Tentori et al., 1988;Tanaka et al, 1992) provide strong evidence for a direct role for IL-2 in thymocyte development. Recent studies analyzing thymocyte development in IL-2-deficient (IL-2-/-) mice have provided more direct evidence for a requirement for IL-2 for normal thymocyte development.…”

Differential Roles of Cytokine Receptors in the Development of Epidermal γδ T Cells

“…Deletion of IL-15, IL-15R␣, or IL-2R␤ results in a block of NK cell development and impaired ␥␦ T cell development in the epithelium (33)(34)(35). Mature V␥3 ϩ thymocytes in the fetal thymus express IL-2R␤, and in utero treatment with anti-IL-2R␤ Ab abrogates DETC in the adult skin (36). IL-2R␤-deficient mice have decreased numbers of ␥␦ IEL (33).…”