The Journal of Experimental Medicine
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Published 1 March 2004. doi:10.1084/jem.20030795
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 5, 725-730
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Brief Definitive Report

 MHC Class II Expression Restricted to CD8{alpha}+ and CD11b+ Dendritic Cells Is Sufficient for Control of Leishmania major

Maria P. Lemos1, Fatima Esquivel2, Phillip Scott2, and Terri M. Laufer1

1 Department of Medicine, and 2 Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104

Address correspondence to Terri M. Laufer, Dept. of Medicine, University of Pennsylvania, 753 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104. Phone: (215) 573-2975; Fax: (215) 573-7599; email: tlaufer{at}mail.med.upenn.edu

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-Aßb, expression is restricted to CD11b+ and CD8{alpha}+ 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 IFN{gamma}. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8{alpha}+ 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.

Key Words: Langerhans cells • CD4 • macrophages • Th1 • antigen presentation


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