Immune function in systemic lupus erythematosus. Impairment of in vitro T-cell proliferation and in vivo antibody response to exogenous antigen.

Gottlieb, Alice B.; Lahita, Robert G.; Chiorazzi, Nicholas; Kunkel, Henry G.

doi:10.1172/jci109388

Cited by 90 publications

(29 citation statements)

References 38 publications

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“…Moreover, these cells presented impaired upregulation of CD83 and IL-12 production after maturation with LPS. In agreement with our findings, it was shown that mature DC from SLE patients present impaired up-regulation of MHCII and are defective in MLRs (51)(52)(53). Also, DC from rheumatoid arthritis patients showed increased production of IL-1, IL-6, TNF-␣, and IL-10 and an altered pattern of chemokine secretion (54,55).…”

Section: Discussionsupporting

confidence: 91%

Immune Complexes Inhibit Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

Laborde¹,

Vanzulli²,

Beigier-Bompadre³

et al. 2007

The Journal of Immunology

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The interaction between immune complexes (IC) and the receptors for the Fc portion of IgG (FcγRs) triggers regulatory and effector functions in the immune system. In this study, we investigated the effects of IC on differentiation, maturation, and functions of human monocyte-derived dendritic cells (DC). When IC were added on day 0, DC generated on day 6 (IC-DC) showed lower levels of CD1a and increased expression of CD14, MHC class II, and the macrophage marker CD68, as compared with normally differentiated DC. The use of specific blocking FcγR mAbs indicated that the effect of IC was exerted mainly through their interaction with FcγRI and to a lesser extend with FcγRII. Immature IC-DC also expressed higher levels of CD83, CD86, and CD40 and the expression of these maturation markers was not further regulated by LPS. The apparent lack of maturation following TLR stimulation was associated with a decreased production of IL-12, normal secretion of IL-10 and CCL22, and increased production of CXCL8 and CCL2. IC-DC displayed low endocytic activity and a reduced ability to induce allogeneic T cell proliferation both at basal and LPS-stimulated conditions. Altogether, these data reveal that IC strongly affect DC differentiation and maturation. Skewing of DC function from Ag presentation to a proinflammatory phenotype by IC resembles the state of activation observed in DC obtained from patients with chronic inflammatory autoimmune disorders, such as systemic lupus erythematosus disease and arthritis. Therefore, the altered maturation of DC induced by IC may be involved in the pathogenesis of autoimmune diseases.

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Section: Discussionsupporting

confidence: 91%

Immune Complexes Inhibit Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

Laborde¹,

Vanzulli²,

Beigier-Bompadre³

et al. 2007

The Journal of Immunology

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“…Because our cohort of patients with SLE had predominantly quiescent disease, this may explain their normal responses to SEB. In addition, previous studies showed decreased proliferation of PBMCs (27)(28)(29), whereas others showed a normal proliferative capacity (30) or heterogeneous results (31).…”

Section: Discussionmentioning

confidence: 95%

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

Holvast¹,

Assen²,

Haan³

et al. 2009

Arthritis & Rheumatism

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Objective. Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE.Methods. Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cellmediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-␥ (IFN␥) enzymelinked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.Results. Prior to vaccination, patients with SLE had fewer IFN␥ spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFN␥-positive CD8؉ T cells. After vaccination, the number of IFN␥ spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4؉ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8؉ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects.Conclusion. In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.

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“…Greatly reduced numbers of T inducerhelper cells in SLE would explain, at least in part, the broad defects in cell-mediated immunity characteristic of this disorder (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

T Lymphocyte Subsets in Systemic Lupus Erythematosus

Bakke

Kirkland

Kitridou

et al. 1983

Arthritis & Rheumatism

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The contribution of immune regulation to the etiology of systemic lupus erythematosus (SLE) is poorly understood. Using the monoclonal antibodies OKT4 and OKTS, we quantitated, by flow cytometry, T inducer/ helper and T cytotoxicfsuppressor cells in patients with SLE. Serologically active patients, who had clinical manifestations such as arthritis or rash and were not receiving prednisone, were characteristically lymphopenic due to a marked reduction in OKT4+ cells. Prednisone therapy produced the same phenomenon. Untreated patients, who were serologically inactive, demonstrated no abnormalities. These studies have thus revealed two presumably independent factors that can produce similar immunoregulatory aberrations.Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by excessive immunoglobulin and autoantibody production. Although B cell function is increased, T cell functions which include delayed hypersensitivity (1-3, mitogenic reactivity (6,7), generation of antigen-specific reactivities (8), and development of nonspecific suppressor (14).We studied 28 patients with SLE who were divided into groups based on corticosteroid therapy and serologic evidence of disease activity. We will describe clinically significant abnormalities in the absolute number and relative proportions of immunoregulatory T cell subsets based upon this classification. PATIENTS AND METHODSPatients. This study included 28 patients (24 females, 4 males) with SLE according to the American Rheumatism Association ( M A ) preliminary criteria (15). Two to 3 patients were randomly selected in the lupus clinic visits each month from April 1981 to April 1982. These patients were then separated into 2 groups based on existing therapy, one receiving more than 10 mg prednisone per day, the other receiving 10 mg or less of prednisone per day. A special attempt was made to isolate newly diagnosed lupus patients being treated with 10 mg or less prednisone per day. During this 1-year period, 11 newly diagnosed patients were seen, but only 6 had 4 or more ARA preliminary criteria; of these 6, only 5 were treated with less than 10 mg prednisone per day.Control groups consisted of 16 women and 5 men with scleroderma and 16 patients with lepromatous leprosy. They will be described in detail elsewhere. Normal individ-

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Immune function in systemic lupus erythematosus. Impairment of in vitro T-cell proliferation and in vivo antibody response to exogenous antigen.

Cited by 90 publications

References 38 publications

Immune Complexes Inhibit Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

Immune Complexes Inhibit Differentiation, Maturation, and Function of Human Monocyte-Derived Dendritic Cells

Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus

T Lymphocyte Subsets in Systemic Lupus Erythematosus

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