Genetic control of murine T cell proliferative responses to Mycobacterium leprae. V. Evidence for cross-reactivity between host antigens and Mycobacterium leprae.
T cell proliferative responses to Mycobacterium leprae were measured by immunization of mice at the base of the tail with Ag and challenging lymphocytes from draining lymph nodes in culture with M. leprae. C57BL/10J and B10.BR mice were identified as low responder mice and the congenic strains B10.M, B10.Q, and B10.AKM as high responders whereas F1 (high x low) hybrid mice were found to be low responders. The cellular basis of low responsiveness did not appear to result from a defect in Ag-presenting cells or the activation of suppressor T cells by M. leprae. The influence of the environment in which T cells developed on responsiveness to M. leprae was analyzed in chimeric mice prepared by irradiating F1(C57BL/10J x B10.M) mice and reconstituting with bone marrow from C57BL/10J, B10.M, or F1 donors. Six weeks later, chimeric mice were immunized with M. leprae, lymph node cells were subsequently prepared, and H-2 phenotyped and challenged in culture with M. leprae Ag. T cell proliferative responses were found to be low in all cases, similar to those observed using lymph node cells from F1 hybrid mice. These results suggested that high responder B10.M lymphocytes developing in the irradiated F1 mice became tolerized to antigenic determinants found on M. leprae. This implied cross-reactive epitopes existed between some mouse strains and M. leprae. Low responsiveness to M. leprae in low responder and F1 hybrid mice may result from tolerance to H-2-encoded Ag that show cross-reactivity with M. leprae.
Harris
D P
DP
Department of Immunobiology, School of Medicine, University of Auckland, New Zealand.
Jones
A G
AG
Wade
S
S
Krahenbuhl
J L
JL
Gillis
T P
TP
Watson
J D
JD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D003429:Cross Reactions / Q000528:radiation effects; D003433:Crosses, Genetic; D004306:Dose-Response Relationship, Immunologic; D007113:Immunity, Innate; D007918:Leprosy / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009166:Mycobacterium leprae / Q000254:growth & development / Q000276:immunology*; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory
D000942:Antigens, Bacterial