The Peyer's patch microenvironment suppresses T cell responses to chemokines and other stimuli.
Immunosurveillance of mucosal sites presents immune cells with challenges not encountered in the periphery. T cells in the gut must distinguish enteric pathogens from innocuous non-self Ag derived from food or commensal bacteria. The mechanisms that regulate T cells in the gut remain incompletely understood. We assessed the effect of the Peyer's patch microenvironment on T cell responses to chemokines. Chemokines are believed to play an important role during T cell priming by facilitating T cell migration into and within lymphoid tissues as well as T cell encounter and interaction with APCs. We found a profound suppression of chemokine-stimulated T cell chemotaxis and actin polymerization in Peyer's patch relative to lymph node. Chemokine hyporesponsiveness is imposed upon T cells within hours of their entry into Peyer's patches and is reversed following their removal. Suppression was not restricted to chemokine stimulation, as T cell responses to Con A and PMA were also suppressed. The global nature of this defect is further underscored by an impairment in calcium mobilization. Evidence indicates that a soluble factor contributes to this hyporesponsiveness, and comparison of Peyer's patches and lymph nodes revealed striking differences in their chemokine and cytokine constitution, indicating a marked Th2 bias in the Peyer's patches. The role of the Th2 microenvironment in mediating suppression is suggested by the ability of Nippostrongylus brasiliensis to elicit hyporesponsiveness in lymph node T cells. The suppressive milieu encountered by T cells in Peyer's patches may be critical for discouraging undesired immune responses and promoting tolerance.
Kellermann
S A
SA
Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304, USA. kellermann_s@abgenix.com
McEvoy
L M
LM
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors
D000199:Actins; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D019707:Receptors, Chemokine