CD4(-CELLS FROM 2,4,6-TRINITROBENZENE SULFONIC-ACID (TNBS)-INDUCED COLITIS RODENTS MIGRATE TO THE RECIPIENTS COLON UPON TRANSFER - DOWN-REGULATION BY CD8(+) T-CELLS() T)

CD4(+) T cells play an important role in the aetiology of inflammatory bowel disease (IBD), but it is not clear which factor(s) cause activa tion of these cells. The aim of this study was to examine the effects of adoptive transfer of splenic (CD4(+)) T cells from TNBS/ethanol-sen sitized donor rats to naive recipients and the migration pattern of tr ansferred T cells. For the transfer experiments, colitis was induced i n rats by colonic administration of TNBS/ethanol. Seventeen days later , either total splenic T cells or CD4(+), or CD8(+) T cells were trans ferred to naive recipients. At days 1, 2 and 3 after transfer, the rec ipients were killed and the migration pattern of the transferred T cel ls was studied, as well as inflammatory cells in several organs, inclu ding the colon. To determine cytokine profiles of the T cells, colitis was induced in mice. Therefore, different combinations of 2,4-dinitro benzene sulfonic acid (DNBS) in ethanol or saline, or ethanol alone we re intrarectally administered. At day 9 after induction of colitis, mi ce were killed and cytokine profiles in the colon were studied by reve rse transcriptase-polymerase chain reaction (RT-PCR) and immunohistoch emistry. The results show that CD4(+) T cells from donor rats with TNB S/ethanol-induced colitis migrate in particular to the colon upon tran sfer to naive recipients, and that this process is down-regulated by C D8(+) T cells. This migration is probably caused by T cell recognition of the colonic bacterial flora and initiates an inflammatory reaction in the recipient's colon, characterized by an increase of the recipie nt's own T cells, macrophages, and neutrophils. In the mice experiment s we showed that a second administration of DNBS/ethanol or ethanol al one, which presumably causes bacterial translocation, results in incre ased numbers of T cells into the colon, accompanied by an increase in Th1 cytokines. These data suggest that Th1 cells recognize the colonic bacterial flora.