Trypanosoma cruzi infection in MHC-deficient mice: further evidence for the role of both class I- and class II-restricted T cells in immune resistance and disease.
The role of T cell population in immune control of Trypanosoma cruzi infection and subsequent development of disease has been examined using gene knockout mice deficient in the expression of either or both class I and Class II MHC. Mice deficient in either class I- or class II-restricted T cell populations show a striking similarity in their mortality rate, parasite load and tissue inflammatory response following infection with the Brazil strain of T. cruzi. In both cases all animals died during the acute phase of the infection with high parasitemias and high parasite loads in the heart and skeletal muscle, but with reduced tissue inflammatory response. Mice deficient in both class I and class II MHC expression demonstrated even higher numbers of circulating and tissue parasites, essentially non-existent tissue inflammatory responses, and succumbed to infection earlier than single-deficient mice. MHC class I-deficient mice which survive into the chronic phase following infection with the M/78 or M/80 clones of T. cruzi have both relatively higher tissue parasite loads and more extensive and severe inflammatory responses than control immunocompetent mice. Immunologically, the acute infection in the double-deficient mice was accompanied by a marked increase in CD4(-)CD8(-)alphabetaTCR+ cells in the spleen. Surprisingly, both class I- and class II-deficient mice produce detectable but sub-normal levels of anti-parasite antibodies while double-deficient mice produced little to no detectable anti-parasite antibody. These results establish the importance of both class I- and class II-restricted T cells in immune control of circulating blood stages and intracellular states of T. cruzi. In addition, this work reinforces the relationship between tissue parasite load and the severity of the inflammatory lesions in chronically infected animals.
Tarleton
R L
RL
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Grusby
M J
MJ
Postan
M
M
Glimcher
L H
LH
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D001769:Blood / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D005434:Flow Cytometry; D006321:Heart / Q000469:parasitology; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007153:Immunologic Deficiency Syndromes; D007249:Inflammation / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000913:Antibodies, Protozoan; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II