T rypanosoma brucei species are protozoan parasites that cause severe disease and death to humans and animals in Africa (1-4). The parasites have developed highly sophisticated mechanisms to escape host immune responses, including antigenic variation of the variant surface glycoprotein (VSG) (3, 5), immunosuppression (4, 6, 7), and splenic B cell depletion (8, 9). For practical and ethical reasons, mouse models have become an alternative and have proven to be a cornerstone for studying African trypanosomiasis of humans and domestic animals (2). BALB/c mice are highly susceptible to T. brucei and Trypanosoma congolense infections, whereas C57BL/6 mice are relatively resistant, as measured by levels of parasitemia, immunosuppression, and survival time (10-12). Immunological experiments are often performed using C57BL/6 mice, because most of the gene-deficient mice available have the C57BL/6 background.Early studies showed that clearance of the parasites takes place mainly in the liver (13,14). Further studies demonstrated that the parasites are cleared by Kupffer cells via phagocytosis (15), which is mediated by IgM as well as IgG antibodies (Abs) specific for VSG (16,17). More recently, using IgM-deficient and B cell-deficient mice, it has been shown that IgG, but not IgM, Abs play a dominant role in the clearance of the parasites (18,19). Gamma interferon (IFN-␥), produced by VSG-specific T cell receptor ␣-positive (TCR␣ ϩ ) CD4 ϩ T cells (20), is critical for host resistance to African trypanosomes (18,(21)(22)(23)(24). It is likely that IFN-␥ exerts its protective effect through macrophage activation, resulting in secretion of tumor necrosis factor alpha (TNF-␣) and nitric oxide, which mediate parasite lysis or death (18,(25)(26)(27). However, overactivation of macrophages driven by excessive production of IFN-␥, particularly in the absence of interleukin-10 (IL-10) signaling, induces liver pathology, which kills the infected mice (15,28,29). As a regulatory cytokine, IL-10 is required to downregulate macrophage activation (15,23,28). Thus, IFN-␥ and IL-10 play crucial roles in protective as well as pathological immune responses during African trypanosomiasis (1, 4). CD4 ϩ and CD8 ϩ T cells are the major potential producers of IFN-␥ and IL-10. Although the important roles of IFN-␥ and IL-10 in the pathogenesis of African trypanosomiasis have been documented, the roles of CD4 ϩ and CD8 ϩ T cells in the development of the disease are not fully understood. In this study, we evaluated the contributions of CD4 ϩ and CD8 ϩ T cells to the pathogenesis of this disease. In particular, we focused on how their contributions were related to IFN-␥ and IL-10.
MATERIALS AND METHODSMice. Female 8-to 10-week-old BALB/c AnNCrlBR (BALB/c) mice and 5-to 6-week-old female outbred Swiss white mice (CD1) were purchased from the National Cancer Institute (Frederick, MD). CD4Ϫ/Ϫ and