Effect of T Cell Modulation on the Translocation of Bacteria from the Gut and Mesenteric Lymph Node

Although the ability of the gut-associated lymphoid tissue (GALT) to respond to orally ingested foreign antigens has been studied extensively, its function in preventing or limiting escape of resident gut bacteria has not been assessed. The following studies were performed to examine what role cell-mediated immunity (CMI) plays in this process. The ability of suppression of CMI to induce escape of gut bacteria (translocation) to the mescnteric lymph node (MLN) in immunocompctent mice whose gut flora was unaltered was examined. Administration of cyclosporine or anti-L3T4 antibody failed to induce translocation of indigenous gut bacteria after 7 or 14 days of treatment. Antithymocyte globulin (ATG) also failed to induce translocation after 7 days of treatment, despite depletion of all Thy 1, Lyt 1, L3T4, and Lyt 2 positive cells from the spleen, MLN, and intestine as demonstrated by immunofluorescent microscopy. Finally, cultures of the MLN, spleen, liver, and peritoneum of T cell-deficient BALB/c nude mice and their heterozygous T cell-replete littermatcs were also sterile, demonstrating that congenital suppression of T CMI also docs not lead to translocation of indigenous gut bacteria. The role of CMI in limiting systemic spread of bacteria that were already translocating to the MLN was also examined. Translocation of Escherichia coli C25 to the MLN was induced by gastrointestinal (GI) monoassociation, which leads to translocation of E. coli C25 to the MLN in 80–100% of mice. Treatment with ATG during monoassociation failed to induce spread of E. coli C25 to the spleen, liver, or peritoneum, despite the same degree of T cell depletion achieved with ATG in the previous experiment. Monoassociation of conventional T cell-deficient BALB/c nude and hetero/ygous mice and germfree T cell-deficient BALB/c nude and heterozygous mice also did not lead to spread of E. coli C25 beyond the MLN. However, in ATG-treated, conventional nude, and germ-free nude mice, the average number of translocating E. coli C25 per MLN was consistently higher. In separate experiments the ability of stimulation of T cell function to inhibit translocation of E. coli C25 was examined. Rccombinant intcrleukin-2, 25,000 units, was administered intraperitoneally every 8 hours during exposure to E. coli C25. This reduced the incidence of translocation of E. coli C25 from 85% to 51% (p = 0.02). Suppression of CMI, either systemically or within the GALT, has n minimal influence on the mechanisms by which the normal gut flora are translocated to the MLN. However, suppression of CMI promotes increased survival of the bacteria that have translocated to the MLN. Conversely, augmentation of T cell function may reduce the number of bacteria that survive in the node, possibly by enhanced bacterial killing within the local environment of the MLN.