Leishmania Major Infection in Major Histocompatibility Complex Class II-Deficient Mice: CD8 + T Cells Do not Mediate a Protective Immune Response

Abstract

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-γ 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.