Intragraft distribution of lymphocytes expressing beta7 integrins after small bowel transplantation in mice.
Lymphocytes with activated beta7 integrins (alphaEbeta7 and alpha4beta7) contribute to inflammatory reactions in the small bowel. Since the selective recruitment of lymphocytes to the lymphoid compartments of the small bowel is controlled by distinct adhesion molecule interactions, a compartment-dependent use of beta7 integrins may influence the rejection response within intestinal transplants. To further delineate the nature of beta7 integrin-mediated graft infiltration, we analysed their expression on T lymphocytes in the heterotopically transplanted small bowel of BALB/c and C57BL/6 mice. Lymphocytes isolated from the epithelium, lamina propria (LP), Peyer's patches (PP), and mesenteric lymph nodes (MLN) were analysed by three-color fluorescence flow cytometry using monoclonal antibodies (mAb) to integrin the subunits, lymphocyte markers, and MHC I of the donor and recipient strains. On postoperative day 5 (POD) after allogeneic small bowel transplantation (SBT), 43% of intraepithelial lymphocytes (IEL) and 63% of LP, 93% of MLN, and 93% of PP lymphocytes were of host origin. In the MLN and PP of allografts, a major infiltrating lymphocyte population consisted of CD8+ cells with increased expression of alpha4beta7 and decreased expression of L-selectin, an adhesion molecule profile characteristic of intestinal effector cell phenotypes. An increase in alpha4beta7 levels was also found on CD8+ host lymphocytes in the LP. The integrin profile of a number of host IEL suggests an ongoing transition from the phenotype of graft infiltrating lymphocytes with high levels of alpha4beta7 and low levels of alphaepsilonbeta7 to that of resident IEL with high levels of alphaepsilonbeta7 and low levels of alpha4beta7. The importance of beta7-mediated lymphocyte trafficking to the graft is attested by the significant reduction in the host lymphocyte population in the LP, PP, and epithelium following the administration of a beta7-blocking mAb to allograft recipients. In conclusion, while the infiltration patterns of lymphocytes may vary between the lymphoid compartments of intestinal allografts, host CD8+ lymphocytes with high levels of alpha4beta7 constitute a major effector cell population that affects the entire graft.
Kellersmann
Richard
R
Experimental Transplantation Immunology, Department of Surgery, University of Würzburg, Oberdürrbacher Str.6, 97080 Würzburg, Germany. kellersmann_r@chirurgie.uni-wuerzburg.de
Ulrichs
Karin
K
Kellersmann
Anne
A
Thiede
Arnulf
A
D000818:Animals; D006084:Graft Rejection / Q000378:metabolism*; D039641:Integrin beta Chains / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000166:cytology / Q000378:metabolism
D039641:Integrin beta Chains; C091368:integrin beta7