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.KeywordsHank Balance Salt SolutionSpontaneous ReleaseCytolytic ActivityLamina Propria LymphocyteOligoclonal ExpansionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.