Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection
Soong, L.; Chang, C.H.; Sun, J.; Longley, B.J.; Ruddle, N.H.; Flavell, R.A.; McMahon-Pratt, D.
Journal of Immunology 158(11): 5374-5383
1997
ISSN/ISBN: 0022-1767 PMID: 9164958 Document Number: 471520
The mechanism(s) underlying the generalized susceptibility of inbred mice strains to Leishmania amazonensis (MHOM/BR/77/LTB0016) infection was studied using mice deficient in either T cell development or in the expression of 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 weeks pi, and at 11 weeks pi had 105-fold fewer parasites in the infected foot compared to the wild-type mice. Similarly, both B6 nude and RAG2 -/- mice failed to develop lesions. However, RAG2 -/- mice reconstituted with naive wild-type CD4+ T cells and beta 2m -/- 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. It is concluded 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.