title: Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection.
abstract: Most inbred strains of mice are susceptible to Leishmania amazonensis infection. We have examined the mechanism(s) underlying this generalized susceptibility using mice deficient in T cell development or in the expression of either MHC class I or class II. In contrast to wild-type C57BL/6 (B6) mice that uniformly developed large ulcerating lesions, mice lacking functional CD4+ T cells (due to targeted disruption of genes for either MHC class II trans-activator or I-A beta) showed no signs of lesion development for up to 12 to 14 wk postinfection and contained significantly lower numbers of parasites in lesions. Similarly, both B6 nude and RAG2 -/- mice failed to develop lesions. However, RAG2 -/- mice reconstituted with naive wild-type CD4+ T cells and beta2m -/- mice did develop lesions. Lesions of MHC class II -/- mice contained minimal numbers of CD8+ T cells, a marked reduction of monocytes/macrophages, and evident extracellular parasites. The inability to mount an inflammatory response in MHC class II -/- mice correlated with the failure to produce lymphokines that lead to the recruitment of monocytes/granulocytes. These results demonstrate that CD4+ T cells are the primary lymphocyte subset that mediates cellular infiltration, lesion pathology, and therefore, susceptibility to L. amazonensis infection. The disease-promoting CD4+ T cells in L. amazonensis-infected mice have the characteristics of Th1 cells. The striking differences in the course of infection between MHC class II -/- mice infected with L. amazonensis and Leishmania major suggest that these parasites may have adapted different strategies regarding the CD4-dependent immune response.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: L
authors.initials: L
authors.lastname: Soong
authors.forename: C H
authors.initials: CH
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: B J
authors.initials: BJ
authors.lastname: Longley
authors.forename: N H
authors.initials: NH
authors.lastname: Ruddle
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
authors.forename: D
authors.initials: D
authors.lastname: McMahon-Pratt
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D007891:Leishmania; D007896:Leishmaniasis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2