News and Publications

Lymphoepithelial Communication in the Intestine

R. Boismenu, Y. Chen, K. Chou, A. El-Sheikh, J. Tryansky

The intestinal mucosa shields the body from the external environment but still allows the intake of essential nutrients. This epithelial barrier is continuously subjected to potentially toxic, infectious, and otherwise harmful agents. Distinct immune mechanisms have evolved to maintain the integrity of this compartment. In particular, T cells belonging to both the and the ß cell lineages are found in close physical association with the mucosa. Previously, we showed that activated intestinal cells but not ß cells produce the epithelial growth factor FGF-7. Interestingly, FGF-7 appears to be the only cytokine expressed by intestinal cells that can support the survival of epithelial cell lines in tissue culture. In addition, we showed that intestinal cells synthesize several chemokines whose function is to recruit inflammatory cells. These findings suggest that intestinal cells and the soluble factors they produce play important roles in maintaining intestinal homeostasis in normal and disease conditions.

ROLE OF CELLS IN INTESTINAL HOMEOSTASIS

We are evaluating the role of intestinal cells in a murine model of colitis induced by feeding the animals dextran sodium sulfate. In this model system, focal areas of disease activity appear within the first 3 days of treatment with dextran sodium sulfate. Large numbers of activated cells accumulate within the affected intestinal segments. In contrast, marked inflammation occurs only after 5 days of treatment.

We are pursuing the hypothesis that local production of chemokines by resident cells is involved in the initiation of this inflammatory response. Using cellular and molecular approaches, we showed that activated cells in the vicinity of intestinal lesions induced by dextran sodium sulfate are a major source of FGF-7 and of several cytokines known to modulate immune responses. In ongoing projects, we will characterize colitis induced by dextran sodium sulfate in a variety of gene-knockout and transgenic mice that have perturbations in cytokine production and T-cell populations. In additional studies, we are determining antigens recognized by intestinal cells.

ROLE OF CD81 IN THYMOCYTE DEVELOPMENT

In collaboration with W.L. Havran, Department of Immunology, we are continuing our investigation of the mechanisms that control the early stages of T-cell development. We previously determined that CD81, a surface protein normally expressed by thymic epithelial cells in the fetal thymus, is involved in the phenotypic conversion of immature CD4^-CD8^- thymocytes to more mature CD4⁺CD8⁺ cells. Currently, we are defining further the phenotype of immature thymocytes capable of interaction with CD81⁺ epithelial cells. This project includes analysis of defined cell-surface molecules, proteins associated with the cell cycle, and rearrangements of the genes for the T-cell receptor in immature thymocytes. In a related study, we are using biochemical and molecular techniques to detect thymocyte surface proteins that recognize CD81.

PUBLICATIONS

Boismenu, R., Havran, W.L. T cells in host defense and epithelial cell biology. Clin. Immunol. Immunopathol. 86:121, 1998.

Boismenu, R., Chen, Y., Havran, W.L. The role of intraepithelial T cells: A gut feeling. Res. Immunol., in press.

Havran, W.L., Chen, Y., Boismenu, R. Innate functions of epithelial T cells. In: Mechanisms of Lymphocyte Activation and Immune Regulation. VII: Molecular Determinants of Microbial Immunity. Gupta, S., Sher, A., Ahmed, R. (Eds.). Plenum, New York, in press.