The Peyer's patch microenvironment suppresses T cell responses to chemokines and other stimuli

Immunosurveillance of mucosal sites presents immune cells with challenges n ot encountered in the periphery. T cells in the gat must distinguish enteri c pathogens from innocuous non-self Ag derived from food or commensal bacte ria. The mechanisms that regulate T cells in the gut remain incompletely un derstood. 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 withi n lymphoid tissues as well as T cell encounter and interaction with APCs. W e found a profound suppression of chemokine-stimulated T cell chemotaxis an d actin polymerization in Peyer's patch relative to lymph node. Chemokine h yporesponsiveness is imposed upon T cells within hours of their entry into Peyer's patches and is reversed following their removal. Suppression was no t restricted to chemokine stimulation, as T cell responses to Con A and PMA , were also suppressed. The global nature of this defect is further undersc ored by an impairment in calcium mobilization. Evidence indicates that a so luble factor contributes to this hyporesponsiveness, and comparison of Peye r's patches and lymph nodes revealed striking differences in their chemokin e and cytokine constitution, indicating a marked Th2 bias in the Peyer's pa tches. The role of the Th2 microenvironment in mediating suppression is sug gested by the ability of Nippostrongylus brasiliensis to elicit hyporespons iveness in lymph node T cells. The suppressive milieu encountered by T cell s in Peyer's patches may be critical for discouraging undesired immune resp onses and promoting tolerance.