GENERATION OF INTESTINAL MUCOSAL LYMPHOCYTES IN SCID MICE RECONSTITUTED WITH MATURE, THYMUS-DERIVED T-CELLS

Transfer of peripheral lymph node lymphocytes to SCID mice leads to th e long term establishment of mucosal T lymphocytes within the epitheli um and lamina propria of the small and large intestines, Analysis of e ngrafted intraepithelial lymphocytes (IEL) showed that they had acquir ed a surface phenotype that in several respects is typical of IEL. In addition, the functional profile of engrafted IEL derived from lymph n ode T cells was similar to that of normal IEL; as the donor-derived T cells exhibited a strong cytolytic activity, a poor proliferative resp onse to mitogenic stimuli, and a tendency to home and expand specifica lly in the intestine upon transfer to secondary SCID recipients, Optim al engraftment of intestinal T cells required bacterial flora, as the number of lymphocytes was greatly reduced in SCID recipients with a re duced flora, These results demonstrate that mature, thymus-derived T c ells can migrate to the intestine and become functionally specialized to the intestinal milieu, The acquisition of phenotypic markers charac teristic of the intestinal microenvironment by engrafted cells suggest s that T cell migration of lymphocytes to the SCID intestine is not ab errant, but it mag reflect processes that are ongoing in immunocompete nt mice, Furthermore, these data suggest that the homing and/or expans ion of typical, thymus derived T cells in the intestine may be driven by luminal Ags such as those derived from bacterial flora.