title: Disparate effects of depletion of CD1d-reactive T cells during early versus late stages of disease in a genetically susceptible model of lupus.
abstract: Some T cells react with lipid antigens bound to antigen-presenting molecule CD1d. Numbers and functions of a subset of such lipid-reactive T cells are reduced in patients with systemic lupus erythematosus (SLE) and their relatives, as well as in genetically susceptible and chemically induced animal models of lupus-like disease. We have reported that the germline deletion of CD1d exacerbates lupus, suggesting a protective role of these cells in the development of lupus. The use of a knockout mouse model in this study, however, did not allow examination of the role of these cells at different stages of disease. Here, we describe an approach to deplete CD1d-dependent T cells, which allowed us to investigate the role of these cells at different stages of disease in genetically lupus-prone NZB/NZW F1 (BWF1) mice. Repeated intravenous injections of large numbers of CD1d-transfected cells resulted in ∼50-75% reduction in these cells, as defined by the expression of CD4, NK1.1 and CD122, and lack of expression of CD62 ligand. TCR γδ (+)NK1.1(+) cells were also reduced in the recipients of CD1d-transfected cells as compared with control recipients. Such depletion of CD1d-reactive T cells in preclinical BWF1 mice resulted in disease acceleration with a significant increase in proteinuria and mortality. In older BWF1 mice having advanced nephritis, however, such depletion of CD1d-reactive T cells resulted in some disease improvement. Taken together, these data as well as our published studies suggest that CD1d-reactive T cells protect against the development of lupus in animal models. However, these cells appear to be unable to suppress established lupus nephritis in these animals, and might even play a disease aggravating role in late stages of disease.
authors: Autoimmunity and Tolerance Laboratory, Department of Medicine/Rheumatology, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, USA.
authors: J
authors: J
authors: Jacinto
authors: P J
authors: PJ
authors: Kim
authors: R R
authors: RR
authors: Singh
mesh_terms: D000367:Age Factors; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d