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 the long term establishment of mucosal T lymphocytes within the epithelium and lamina propria of the small and large intestines. Analysis of engrafted intraepithelial lymphocytes (IEL) showed that they had acquired a surface phenotype that in several respects is typical of IEL. In addition, the functional profile of engrafted IEL derived from lymph node T cells was similar to that of normal IEL; as the donor-derived T cells exhibited a strong cytolytic activity, a poor proliferative response to mitogenic stimuli, and a tendency to home and expand specifically in the intestine upon transfer to secondary SCID recipients. Optimal engraftment of intestinal T cells required bacterial flora, as the number of lymphocytes was greatly reduced in SCID recipients with a reduced flora. These results demonstrate that mature, thymus-derived T cells can migrate to the intestine and become functionally specialized to the intestinal milieu. The acquisition of phenotypic markers characteristic of the intestinal microenvironment by engrafted cells suggests that T cell migration of lymphocytes to the SCID intestine is not aberrant, but it may reflect processes that are ongoing in immunocompetent mice. Furthermore, these data suggest that the homing and/or expansion of typical, thymus-derived T cells in the intestine may be driven by luminal Ags such as those derived from bacterial flora.
Camerini
V
V
Department of Pediatrics, University of Virginia, Charlottesville 22908, USA.
Sydora
B C
BC
Aranda
R
R
Nguyen
C
C
MacLean
C
C
McBride
W H
WH
Kronenberg
M
M
D000818:Animals; D001419:Bacteria / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*