Lipopolysaccharide (LPS) regulation of the immune response: T lymphocytes from normal mice suppress mitogenic and immunogenic responses to LPS
McGhee, J.R.; Kiyono, H.; Michalek, S.M.; Babb, J.L.; Rosenstreich, D.L.; Mergenhagen, S.E.
Journal of Immunology 124(4): 1603-1611
1980
ISSN/ISBN: 0022-1767 PMID: 6965952 Document Number: 155726
The in vitro immune responsiveness of cells from germfree (GF) mice was investigated by employing lectins and endotoxin. Splenocytes from GF, when compared with those from conventional (Conv), mice manifested similar responses to the T responses after TNP-LPS immunization. To determine the nature of the cell(s) involved in this suppression, macrophages (M.vphi.) and purified lymphocytes were derived from GF and Conv spleens, and various cell combinations were tested for their mitogenic and immunogenic responsiveness to LPS. No apparent differences in anti-TNP PFC and mitogenic responses could be detected between GF and Conv M.vphi. when tested with T and B cells derived from GF mice. However, lower responses were always seen with Conv T and B cells and GF or Conv M.vphi., suggesting a lymphocyte origin for suppression. Purified T cells from Conv spleen or Peyer's patches significantly reduced mitogenic and TNP-LPS immune responses in GF spleen cell cultures. The presence of T suppressor cells was further supported by the observation that GF and nude mice exhibited higher responses to TNP-LPS. This evidence, taken together, suggests that the normal Gram-negative gut flora induces, possibly via lipid A, the production of a T cell population that regulates B cell responses to bacterial endotoxin.