Intestinal T cells function broadly to maintain gut homeostasis. Better understanding of their developmental pathways may lend new insight into the pathogenesis of intestinal inflammatory diseases. The origins of intestinal intraepithelial lymphocytes (IEL) remain controversial as more and more evidence supports the theory that a subset of IEL in mice develops via a non-thymic pathway centered in the gut, suggesting the gut functions as a primary lymphoid organ. Distinct clusters of cells bearing a T cell progenitor phenotype called cryptopatch (CP) aggregates, , are attractive as sites for intestinal T cell development. The central hypothesis of this research proposal is that CP aggregates are a key component in the non-thymic developmental pathway of IEL.
The specific aims of this proposal are 1.) to prove that CP aggregate formation is independent of the presence of a thymus by examining small intestines from neonatally thymectomized (NTX) mice following immunohistochemical staining; and 2.) To determine the progenitor potential of cells within CP aggregates by analyzing cDNA made from these cells for expression of lymphocyte specific genes involved in T cell receptor (TCR) gene rearrangement indicating commitment to the T cell lineage and for the presence of TCR gene rearrangements in normal and NTX mice.
