Cytotoxic Activity of T Cells Expressing Different T-Cell Receptor Variable Gene Products in the Intestinal Mucosa

Abstract

T cells recognize foreign antigen via the heterodimeric T-cell receptor (TCR).^1,2 The peripheral TCR repertoire is shaped via positive and negative selection processes that influence T-cell maturation in the thymus.^3,4 There is increasing evidence that there are modifications of this repertoire by extrathymic events. In the mouse there is evidence that there exists an extrathymic pathway of T lymphocyte development and that this lineage acquires its TCR repertoire via selection processes that occur outside of the thymus.^5-7 Recent studies examining TCR expression by PCR analysis of mRNA in human mucosal T cells, have found skewing of TCR variable gene usage and oligoclonal expansion when compared to peripheral blood T cells.^8,9 These findings suggest that local factors in the intestinal mucosa influence the not only selective homing, but also expansion or selection of T cells bearing certain TCR variable regions genes. The aim of this study was to examine and compare the functional activity of the different TCR V-gene bearing subsets of mucosal and peripheral T cells from the same individual. Our results showed that the cytolytic activity measured in a redirected cytotoxicity assay, using a panel of 7 monoclonal antibodies specific for different TCR V gene products in mucosal T cells differs from that detected in the peripheral blood T cells from the same individual.