Increased Interleukin-4 Production by NK T Cells in Systemic Lupus Erythematosus

Funauchi, Masanori; Yu, Hong-Jeng; Sugiyama, Masafumi; Ikoma, Shinya; Ohno, Motoki; Kinoshita, Koji; Hamada, Kinya; Kanamaru, Akihisa

doi:10.1006/clim.1999.4742

Cited by 30 publications

(23 citation statements)

References 29 publications

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“…The data confirm the previous finding that DN T cells from SLE patients produce greater IL-4 than DN T cells from healthy donors (26) and extend them to show that some of these IL-4-producing DN T cells are CD1c restricted. Those DN T cell lines that recognized CD1c directly were selected for the studies evaluating their ability to promote IgG production described below.…”

Section: Dn T Cells From Sle Patients and Healthy Donors Recognize CDsupporting

confidence: 90%

“…Evidence for T helper activity in SLE DN T cells expressing either ␣␤ or ␥␦ T cells exists (5,26,27), although the role of CD1 in this helper activity has not been evaluated. Therefore, we derived DN T cell lines, regardless of TCR expression, from the blood of SLE patients and healthy donors by immunomagnetic depletion of CD4 and CD8 T cells.…”

Section: Dn T Cells From Sle Patients But Not Those From Healthy Donmentioning

confidence: 99%

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Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Sieling¹,

Porcelli

Duong³

et al. 2000

The Journal of Immunology

118

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To understand the mechanism of T cell help for IgG production in systemic lupus erythematosus (SLE) we investigated the response of CD4- and CD8-negative (double-negative (DN)) T cells because 1) DN T cells are present at unusually high frequency in patients with SLE and can induce pathogenic autoantibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag-presenting molecules; and 3) CD1c is expressed on a population of circulating B cells. We derived DN T cell lines from SLE patients and healthy individuals. In the presence of CD1+ APCs, DN T cell lines from SLE patients produced both IL-4 and IFN-γ, whereas DN T cells from healthy donors produced IFN-γ, but no IL-4. In general, cells from patients with highly active disease produced high levels of IFN-γ; cells from those with little activity produced high IL-4. Coculture of CD1c-directly reactive T cells from healthy donors with CD1c+ B cells elicited IgM Abs, but little or no IgG. In contrast, CD1c-directly reactive T cells from SLE patients induced isotype switching, with a striking increase in IgG production. Neutralizing Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c+ B cells, further indicating that CD1c mediated the T and B cell interaction. IgG production was also inhibited by neutralizing Abs to IL-4, correlating with the cytokine pattern of DN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c+ B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.

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Section: Dn T Cells From Sle Patients and Healthy Donors Recognize CDsupporting

confidence: 90%

Section: Dn T Cells From Sle Patients But Not Those From Healthy Donmentioning

confidence: 99%

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Sieling¹,

Porcelli

Duong³

et al. 2000

The Journal of Immunology

118

View full text Add to dashboard Cite

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“…A similar mechanism may also operate in (NZB×NZW) F 1 mice, as their splenic CD1 high B cells produce significantly more anti-dsDNA antibody than CD1 low/int B cells, and injection of an antiCD1d mAb ameliorates disease [65]. These findings are consistent with those obtained in human SLE patients that populations of CD4 -CD8 -TCRαβ + T cells, which induce production of anti-dsDNA Abs [66], and IL-4 producing NKT cells are markedly expanded [67]. Again, some of these properties may be associated with CD1-restricted T cells that do not express the canonical TCR, for example, those T cells that are restricted to CD1c [68].…”

Section: Role Of Nkt Cells In Autoimmune Diseasesupporting

confidence: 80%

Regulation of autoimmune disease by natural killer T cells

et al. 2002

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Natural killer T (NKT) cells express phenotypic characteristics shared by conventional natural killer cells and T cells, and reside in several primary and secondary lymphoid as well as nonlymphoid organs. Although these cells possess important effector functions in immunity against cancer and microbial pathogens, their immunoregulatory function has received much recent attention. There is convincing evidence to suggest a regulatory role for these cells in the control of susceptibility to autoimmune disease. NKT cells are reduced in number and function in autoimmune disease prone mice and humans. Studies conducted in mice have shown that transfer of NKT cells to disease-susceptible recipients prevents the development of autoimmune disease. The recent discovery that alpha-galactosylceramide, a glycolipid, can specifically target NKT cells expressing the invariant T cell receptor (TCR) to proliferate and produce an array of regulatory cytokines and chemokines has generated considerable interest to utilize these cells as targets of new therapeutic interventions for the immunoregulation of autoimmune disease

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“…Increased in vitro production of IL‐4 in lupus patients compared with healthy controls was reported by some investigators (45, 46), whereas others found reduced IL‐4 production in patients (47) or no difference between patients and controls (19, 28, 48). In a longitudinal study of 20 patients with SLE (49), serum IL‐4 levels were elevated, but no correlation with SLEDAI scores was found.…”

Section: Candidate Biomarkers Of Lupus Activitymentioning

confidence: 87%