The relative contribution of antibody production and CD8+ T cell function to immune control of Trypanosoma cruzi.
The life cycle of the protozoan parasite Trypanosoma cruzi in mammalian hosts includes both non-dividing trypomastigote forms which circulate in the blood and replicating intracellular amastigotes which reside within the cytoplasm of a variety of host cells. In this study we have used mice with induced mutations in genes responsible for either antibody production or cytolytic T lymphocyte (CTL) function to examine the relative contributions of these effector mechanisms to control of T. cruzi. Mice deficient in the production of antibodies exhibited a delay in the rise in acute phase parasitaemia and an extended time to death relative to mice lacking CD8+ T cells. Nevertheless, B cell deficient mice eventually succumbed to the infection. Prior infection with an avirulent strain of T. cruzi failed to protect either CD8+ T cell-deficient mice or B cell deficient mice from challenge infection with virulent parasites. In contrast, mice with disruptions in the genes controlling perforin- or granzyme B-mediated cytolytic pathways had parasitaemia and mortality rates similar to wild-type mice and were protected from secondary infection by prior exposure to avirulent parasites. These results 1) confirm that antibody production, although secondary in importance to cellular responses, is nevertheless absolutely required and 2) perforin- or granzyme B-mediated lytic pathways are not required for control of T. cruzi infection.
Kumar
S
S
Department of Cellular Biology, University of Georgia, Athens 30602, USA.
Tarleton
R L
RL
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D053804:Granzymes; D008285:Major Histocompatibility Complex / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000913:Antibodies, Protozoan; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases