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. 2004 Mar 1;199(5):725-30.
doi: 10.1084/jem.20030795.

MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic cells is sufficient for control of Leishmania major

Maria P Lemos  1 , Fatima Esquivel, Phillip Scott, Terri M Laufer
Affiliations

"VSports" MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic cells is sufficient for control of Leishmania major

"V体育ios版" Maria P Lemos et al. J Exp Med. .

Abstract (VSports最新版本)

Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)-dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II-positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)gamma-producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Abeta(b), expression is restricted to CD11b+ and CD8alpha+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II-negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNgamma. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8alpha+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection. VSports手机版.

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Figures

Figure 1.
Figure 1.
LCs, B cells, and macrophages lack MHC II expression in CD11c/Aβ b mice. (A) MHC II expression on LCs (CD11c+ FITC+) or resident LN DCs (CD11c+ FITC−) obtained from the draining LNs of mice after epidermal irritation (n = 3 per genotype). (B–D) MHC II levels on APCs harvested from draining LNs of mice infected with L. major 4–7 wk earlier. (B) CD11b+ CD11c− macrophages. (C) CD45R+ B cells. (D) CD11c+ DCs. Histograms correspond to representative Aβ b−/− (light gray with dashed line), CD11c/Aβ b (black line), and Aβ b+/− (dark gray) mice.
Figure 2.
Figure 2.
CD8α+ and CD11b+ DC antigen presentation is sufficient for control of L. major lesions. (A) Footpad swelling in infected Aβ b−/−, CD11c/Aβ b, Aβ b+/−, and Aβ b+/+ TCRα−/− mice that received CD45.1+ T cells before infection (n = 5 mice/genotype). (B) Parasite load at 6–9 wk after infection expressed as logarithm of parasite counts. Standard error of 4–7 mice/genotype is indicated. There was no difference in pathogen clearance amongst CD11c/Aβ b, Aβ b+/−, and TCRα−/− mice, but all had significantly lower parasite loads than I-Aβ b−/− mice (P < 0.002).
Figure 3.
Figure 3.
DCs mediate L. major–specific Th1 differentiation. (A) Intracellular IFNγ staining from CD4 T cells 9 wk after footpad infection. Transferred CD45.1+ cells and endogenous CD45.1− CD4+ T cells are depicted. (n = 5–8 mice/genotype). Under each dot plot, the total number of CD4+ T cells recovered from the harvested LNs is shown. (B) IFNγ production from purified splenic CD4+ T cells after 72 h of incubation with the indicated APCs, in the presence or absence of soluble L. major antigen (SLA). CD4+ T cells from three mice of each genotype were combined. This experiment is representative of three individual experiments.
Figure 4.
Figure 4.
Macrophage effector functions are MHC II–independent. Footpads and popliteal LNs were harvested 4 wk after infection. (A) CD40 levels on draining LN macrophages (CD11b+ CD11c− Gr1−). The dashed line depicts staining by an isotype control. (B) Intracellular iNOS in CD11b+ CD11c− macrophages from popliteal LNs. (C and D) Immunostaining of footpad lesions stained for (C) CD4 and MHC II and iNOS (D).
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References

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