Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus

Stekman, Ivan L.; Blasini, Ana M.; Leon‐Ponte, Matilde; Baroja, Miren L.; Abadi, Isaac; Rodríguez, M.

doi:10.1002/art.1780340411

Cited by 30 publications

(21 citation statements)

References 36 publications

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“…First, we found in preliminary experiments a reproducible defective proliferative response to PHA and IL-2 production in SLE T cells that was consistent with previously published observations [1,2]. Second, controversial data have been reported regarding the response of SLE T cells to anti-CD3 MoAbs [20][21][22][23]. This is due to the use of varying anti-CD3 MoAbs of different isotypes, epitope specificity and culture conditions.…”

Section: Discussionsupporting

confidence: 90%

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Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients

García-Cózar

Molina

Cuadrado

et al. 1996

Clinical and Experimental Immunology

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SUMMARYDefective T cell functions, including IL-2 production and proliferation, have been shown in SLE patients. After T cell stimulation (first signal), a costimulatory signal (second signal) is required to achieve complete T cell activation. Main costimulatory signals are provided to T cells by B7 antigens (CD80 and CD86, expressed on antigen-presenting cells (APC)) upon interaction with its receptor, the CD28 molecule expressed on T cells. The aim of this study was to investigate the role of CD28/B7 interactions in the impaired T cell responses of SLE patients. We show that stimulation of T cells with phytohaemagglutinin (PHA) in the presence, but not in the absence, of anti-CD28 MoAb or B7 cells results in tyrosine phosphorylation of specific substrates, transcription of mRNA and production of IL-2 that is indistinguishable in SLE patients and healthy controls. Moreover, proliferation of costimulated T cells from SLE and controls was specifically abrogated by blocking the CD28/B7 interactions by means of addition to the culture of the CTLA4-Ig fusion protein. However, in most patients activated APC failed to up-regulate B7 molecules, giving rise to ineffective costimulatory signalling to T cells. These results indicate that the CD28/B7 costimulatory pathway is defective in SLE patients.

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Section: Discussionsupporting

confidence: 90%

“…For this purpose, we selected phytohaemagglutinin (PHA) as stimulus, since it is generally accepted that SLE T cells consistently show a reduced ability to produce IL-2 and to proliferate in response to this mitogen. Conversely, contradictory data have been obtained when SLE T cells are challenged with anti-CD3 MoAb [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients

García-Cózar

Molina

Cuadrado

et al. 1996

Clinical and Experimental Immunology

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“…Fresh medium was added and the cells were (re-)stimulated with 10 µg phytohemagglutinin-M (PHA-M)/ml (Sigma) for 24 h. In separate wells, fresh PBMC (1 × 10 6 cells/ml) were also stimulated with 10 µg/ml PHA-M for 72 h for comparisons. For this study, we chose to use the PHA-M stimulation based on: (1) preliminary experiments that demonstrated reproducible decreases in SLE patient T-lymphocyte (particularly CD3 + CD4 + and CD4 + CD45RO + ) proliferative responses and IL-2 production after PHA-M stimulation (outcomes consistent with published observations; Alcocer-Varela and AlarconSegovia, 1982;Linker-Israeli et al, 1983); and (2) controversial data that have been reported regarding responses of SLE T-lymphocytes to anti-CD3 monoclonal antibodies (see Stekman et al, 1991;Blasini et al, 1993).…”

Section: Stimulation Of Pbmcsupporting

confidence: 57%

Alterations in T-lymphocyte sub-set profiles and cytokine secretion by PBMC of systemic lupus erythematosus patients uponin vitroexposure to organochlorine pesticides

Dar

Das

Ramachandran

et al. 2012

Journal of Immunotoxicology

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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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Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus

Cited by 30 publications

References 36 publications

Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients

Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients

Alterations in T-lymphocyte sub-set profiles and cytokine secretion by PBMC of systemic lupus erythematosus patients uponin vitroexposure to organochlorine pesticides

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

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