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 journalArticle

129 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 - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Soong, L., Chang, C. H., Sun, J., Longley, B. J., Ruddle, N. H., Flavell, R. A., & McMahon-Pratt, D. (1997). Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection. Journal of Immunology, 158(11), 5374-5383.