Leishmania major infection in major histocompatibility complex class II-deficient mice: CD8+ T cells do not mediate a protective immune response.
In order to evaluate the role of CD8+ T cells in cutaneous leishmaniasis, major histocompatibility complex (MHC) class II-deficient mice of C57BL/6 background lacking functional CD4+ T cells were infected with Leishmania major. In contrast to C57BL/6 wild-type mice which are resistant to infection with L. major, these mice developed severe skin lesions that did not heal. In comparison to susceptible BALB/c mice, however, lesion development in MHC class II-deficient mice was very much retarded, even though the increase in the parasite load in lymphoid organs was only slightly delayed. Lymph node cells from L. major-infected MHC class II-deficient mice produced very low levels of interferon-gamma upon stimulation with L. major antigen, whereas the response to the mitogen concanavalin A was not impaired. Interestingly, they did not release lymphokines associated with disease exacerbation (interleukin 4 and interleukin 10) either, suggesting that the delayed lesion development is caused by the lack of disease-promoting CD4+ cells rather than by the presence of protective CD8+ cells. The lack of L. major-reactive immunoglobulins in the serum of infected MHC class II-deficient mice indicates that B cells also cannot respond to parasite antigens in the absence of MHC class II-mediated helper signals. The data demonstrate that MHC class II-deficient mice are unable to restrict the spreading of L. major, although they contain highly increased proportions of CD8+ T cells. Thus, MHC class II-restricted immune responses, most likely mediated by functional CD4+ T cells, are essential for the control of primary infections with L. major.
Erb
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K
Blank
C
C
Ritter
U
U
Bluethmann
H
H
Moll
H
H
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology* / Q000469:parasitology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D000949:Histocompatibility Antigens Class II