Normally occurring NKG2D+CD4+ T cells are immunosuppressive and inversely correlated with disease activity in juvenile-onset lupus.

Publication Type:

Journal Article

Source:

The Journal of experimental medicine, Volume 206, Issue 4, p.793-805 (2009)

Keywords:

2009, Age of Onset, Antigens, CD, Antigens, CD4, CD4-Positive T-Lymphocytes, Center-Authored Paper, Clinical Research Division, Cytokine Analysis Core Facility, Cytokines, Fetal Blood, Flow Cytometry Core Facility, Genomics Core Facility, Humans, Immunologic Memory, Infant, Newborn, Interleukin-10, Killer Cells, Natural, Lupus Erythematosus, Systemic, NK Cell Lectin-Like Receptor Subfamily K, Reference Values, Shared Resources, T-Lymphocyte Subsets, T-Lymphocytes, Transforming Growth Factor beta

Abstract:

The NKG2D receptor stimulates natural killer cell and T cell responses upon engagement of ligands associated with malignancies and certain autoimmune diseases. However, conditions of persistent NKG2D ligand expression can lead to immunosuppression. In cancer patients, tumor expression and shedding of the MHC class I-related chain A (MICA) ligand of NKG2D drives proliferative expansions of NKG2D(+)CD4(+) T cells that produce interleukin-10 (IL-10) and transforming growth factor-beta, as well as Fas ligand, which inhibits bystander T cell proliferation in vitro. Here, we show that increased frequencies of functionally equivalent NKG2D(+)CD4(+) T cells are inversely correlated with disease activity in juvenile-onset systemic lupus erythematosus (SLE), suggesting that these T cells may have regulatory effects. The NKG2D(+)CD4(+) T cells correspond to a normally occurring small CD4 T cell subset that is autoreactive, primed to produce IL-10, and clearly distinct from proinflammatory and cytolytic CD4 T cells with cytokine-induced NKG2D expression that occur in rheumatoid arthritis and Crohn's disease. As classical regulatory T cell functions are typically impaired in SLE, it may be clinically significant that the immunosuppressive NKG2D(+)CD4(+) T cells appear functionally uncompromised in this disease.