title: Regulatory interactions between macrophages and T cells in Mycobacterium lepraemurium-specific T-cell activation.
abstract: The antigen-specific proliferative response of draining lymph node cells was found to follow a similar pattern in both C57BL and BALB/c mice following subcutaneous infection with Mycobacterium lepraemurium (MLM), although the two strains differed in their ability to control bacterial growth at the site of infection. The proliferative response, which was maximal 1-2 weeks postinfection, was T-cell dependent as it was abrogated with anti-Thy 1.2 + C treatment. The response was also abrogated by pretreatment with anti-Lyt 1.2 + C and slightly reduced by treatment with anti-Lyt 2.2 + C. The decline in T-cell responsiveness, at least from 4 to 8 weeks postinfection, may have been associated with prostaglandin production by inflammatory macrophages, as it was partially restored by addition of indomethacin. Also highly purified T lymphocytes from lymph nodes taken 6-8 weeks postinfection gave a strong antigen-specific proliferative response when reconstituted with optimal numbers of syngeneic antigen-presenting cells from uninfected mice. Proliferation was inhibited by peritoneal macrophages from Corynebacterium parvum-pretreated mice and macrophages from C57BL but not BALB/c mice infected with M. lepraemurium which had been elicited with heat-killed (HK) MLM and thioglycollate. Resident peritoneal macrophages from both C57BL and BALB/c mice infected subcutaneously with M. lepraemurium were slightly more inhibitory than normal macrophages but not as inhibitory as macrophages from C. parvum-pretreated mice. Macrophage-dependent inhibition of T-cell proliferation was partially reversed by addition of indomethacin, suggesting these cells were not defective in processing and presentation of HK-MLM antigens, and that the inhibitory effects were associated with prostaglandin production. Resident peritoneal macrophages from both C57BL and BALB/c mice infected subcutaneously with M. lepraemurium produced comparable or slightly elevated levels of IL-1 on stimulation with LPS or HK-MLM.
authors.affiliation: Laboratory for Leprosy and Mycobacterial Research, National Institute for Medical Research, London, England.
authors.forename: S J
authors.initials: SJ
authors.lastname: Brett
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000276:immunology*; D009167:Mycobacterium lepraemurium / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology; D011425:Propionibacterium acnes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007375:Interleukin-1; D007213:Indomethacin