Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection

Lynn Soong, Cheong Hee Chang, Jiaren Sun, B. Jack Longley, Nancy H. Ruddle, Richard A. Flavell, Diane McMahon-Pratt

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

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-Aβ) 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 β2m -/- 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. amazonens/s-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.

Original languageEnglish (US)
Pages (from-to)5374-5383
Number of pages10
JournalJournal of Immunology
Volume158
Issue number11
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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