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,
*
Division of Dermatology,
Department of Microbiology and Immunology, and
Molecular Biology Institute, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095;
§
Service de Dermatologie, Hopital Edouard Herriot, Lyon, France;
¶
Department of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, MA 02115;
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RMF Dictagene S.A., Lausanne, Switzerland;
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Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL 33101; and
**
Section of Dermatology and University of Southern California School of Medicine, Los Angeles, CA 90033
Both the CD4-CD8- (double negative) and
CD4-CD8+ T cell lineages have been shown to
contain T cells which recognize microbial lipid and glycolipid Ags in
the context of human CD1 molecules. To determine whether T cells
expressing the CD4 coreceptor could recognize Ag in the context of CD1,
we derived CD4+ T cell lines from the lesions of leprosy
patients. We identified three CD4+ Mycobacterium
leprae-reactive, CD1-restricted T cell lines: two CD1b
restricted and one CD1c restricted. These T cell lines recognize
mycobacterial Ags, one of which has not been previously described for
CD1-restricted T cells. The response of CD4+ CD1-restricted
T cells, unlike MHC class II-restricted T cells, was not inhibited by
anti-CD4 mAb, suggesting that the CD4 coreceptor does not impact
positive or negative selection of CD1-restricted T cells. The
CD4+ CD1-restricted T cell lines produced IFN-
and
GM-CSF, the Th1 pattern of cytokines required for cell-mediated
immunity against intracellular pathogens, but no detectable IL-4. The
existence of CD4+ CD1-restricted T cells that produce a Th1
cytokine pattern suggests a contributory role in immunity to
mycobacterial infection.
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