Developmental expression of the alpha IEL beta 7 integrin on T cell receptor gamma delta and T cell receptor alpha

L Lefrançois1, T A Barrett, W L Havran

  • 1Department of Medicine, University of Connecticut Health Center, Farmington 06030.

A novel monoclonal antibody, 2E7, was shown by immunoprecipitation to be reactive with the alpha IEL beta 7 integrin and was employed to analyze the expression of this integrin in lymphocyte subsets and during T cell ontogeny. In adult lymph nodes, alpha IEL was expressed at low levels by 40-70% of CD8+ T cells and < 5% of CD4+ T cells. However, virtually all intestinal intraepithelial lymphocytes and approximately 20% of lamina propria CD4+ T cells were 2E7+, indicating a preferential expression of this integrin on mucosal T cells. Examination of alpha IEL integrin expression during thymus ontogeny revealed that approximately 3-5% of fetal or adult thymocytes were 2E7+. Interestingly, early in fetal thymus ontogeny, approximately 40% of 2E7+ cells expressed T cell receptor (TcR)-gamma delta and this subset persisted through birth. A developmental switch occurred such that 2E7+ TcR- CD4-8+ cells detected on fetal day 19 were followed by 2E7+ TcR-alpha beta CD4-8+ cells in the neonatal thymus. The latter population persisted throughout thymus ontogeny into adulthood. Interestingly, a subset of TcR-gamma delta V gamma 3+ day 16 fetal thymocyte dendritic epidermal cell (DEC) precursors were 2E7+, but all mature DEC expressed high levels of alpha IEL integrin, suggesting that the alpha IEL integrin was acquired late in DEC maturation. This possibility was strengthened by immunohistochemical localization of the majority of 2E7+ gamma delta and alpha beta T cells to the medullary regions of the thymus. Overall, the results demonstrate a developmentally ordered expression pattern of the alpha IEL beta 7 integrin that suggests a common function for this integrin during TcR-gamma delta and -alpha beta CD4-8+ T cell thymocyte development or perhaps in effector functions for these subsets.

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