Antigen-specific Th1 but not Th2 cells provide protection from lethal Trypanosoma cruzi infection in mice.
Infection with Trypanosoma cruzi results in the development of both type 1 and type 2 patterns of cytokine responses during acute and chronic stages of infection. To investigate the role of Th1 and Th2 subsets of CD4(+) T cells in determining the outcome of T. cruzi infection in mice, we have developed T. cruzi clones that express OVA and have used OVA-specific TCR-transgenic T cells to generate OVA-specific Th1 and Th2 cells. BALB/c mice receiving 10(7) OVA-specific Th1 cells and then challenged with OVA-expressing T. cruzi G-OVA.GPI showed significantly lower parasitemia and increased survival in comparison to mice that received no cells. In contrast, recipients of OVA-specific Th2 cells developed higher parasitemias, exhibited higher tissue parasitism and inflammation, and had higher mortality than recipients of Th1 cells after infection with T. cruzi G-OVA.GPI. Mice receiving a mixture of both Th1 and Th2 OVA-specific cells also were not protected from lethal challenge. The protective effect of the OVA-specific Th1 cells was OVA dependent as shown by the fact that transfer of OVA-specific Th1 or Th2 cells failed to alter the course of infection or disease in mice challenged with wild-type T. cruzi. Immunohistochemical analysis of OVA-specific Th1 and Th2 cells at 4, 15, and 30 days postinfection revealed the persistence and expansion of these cells in mice challenged with T. cruzi G-OVA.GPI but not in mice infected with wild-type T. cruzi. We conclude that transfer of Ag-specific Th1 cells but not Th2 cells protect mice from a lethal infection with T. cruzi.
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
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Kumar
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Tarleton
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D017261:Glycosylphosphatidylinositols / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D017261:Glycosylphosphatidylinositols; D010047:Ovalbumin