Effect of CD28 Antibody on T Cells from Patients with Systemic Lupus Erythematosus

Alvarado, C.; Alcocer‐Varela, Jorge; Llórente, Luis; Richaud‐Patin, Yvonne; Cerbón, M A; Alarcón‐Segovia, Donato

doi:10.1006/jaut.1994.1060

Cited by 19 publications

(14 citation statements)

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“…In respect of T cell lymphopenia, certain T cell subsets may be affected selectively by these three factors. Consistent with the studies using two-colour analysis by Alvarado et al [46], we demonstrated strictly that CD28 T cells are eliminated selectively in SLE. Sfikakis et al [47] suggested that the decrease of CD28 8 T cells in peripheral blood of rheumatoid arthritis (RA) patients might result from the migration of these cells to active sites of inflammation, from the comparative examination of both peripheral blood and synovial fluid T cells in RA patients.…”

Section: Discussionsupporting

confidence: 93%

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Kaneko

Saito

Hashimoto

et al. 1996

Clinical and Experimental Immunology

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SUMMARYCD28 on T cells provides a potent costimulatory signal for T cell activation. Down-regulation of CD28 on peripheral T cells has been reported in certain clinical conditions, but full studies on the mechanism and biological significance have not been performed. Our extensive phenotype analysis of peripheral blood lymphocytes (PBL) from SLE patients revealed that the absolute number of CD28 T cells of both CD4 and CD8 phenotypes was selectively decreased, while that of CD28 ÿ T cells was maintained. CD28 T cells from SLE patients exhibited mostly normal proliferative responses to both CD28-dependent and -independent stimulations. In contrast, CD28 ÿ T cells were hyporesponsive to anti-CD3 stimulation in both SLE and normal controls. These results implied that the selective decrease of CD28 T cells in SLE does not result from a hyporesponsiveness of CD28 T cells. To investigate the reason for the selective loss of CD28 T cells, we determined the appearance of apoptotic cells in culture with or without anti-CD3 stimulation. Apoptotic cells defined by merocyanine (MC)540 were gradually increased from 12 h to 24 h. Anti-CD3-induced apoptosis of CD28 T cells was significantly accelerated in SLE, whereas apoptosis of CD28 ÿ T cells was hardly detected in both SLE and normal controls. Comparative analysis between CD28 and CD28 ÿ T cells on CD95 (Fas) and Bcl-2 expression, which are related to activation-induced cell death (AICD), did not show a major difference, although CTLA4, which has been demonstrated to transmit an apoptosis-inducing signal, was expressed only on CD28 T cells. Our results suggest that CD28-mediated costimulation influences T cell susceptibility to AICD and may be involved in T cell lymphopenia in SLE.

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Section: Discussionsupporting

confidence: 93%

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Kaneko

Saito

Hashimoto

et al. 1996

Clinical and Experimental Immunology

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“…In patients with either active or inactive disease, the mean percentages of CD28 § peripheral blood T cells of both CD4 § and CD8 § subsets are decreased (50,51), although with a remarkable variation in individual SLE patients (range 1-50%), in contrast to normals (range 1-15%) (51). Circulating CD28-T cells in SLE patients are significantly increased (51).…”

Section: Cd28/ctla4:cd80/cd86 Interaction In Lupusmentioning

confidence: 96%

“…Lymphocytes from patients with active disease show increased CD28 mRNA compared to normal subjects (50). Anti-CD3-induced apoptotic death of CD28 § T cells is significantly accelerated in vitro in SLE providing a possible explanation for the loss of these cells from the peripheral blood in vivo, whereas apoptosis of CD28-T cells is hardly detected either in patients with SLE or in normal persons (51).…”

Section: Cd28/ctla4:cd80/cd86 Interaction In Lupusmentioning

confidence: 98%

Immune cell signaling aberrations in human lupus

1998

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A large array of heterogeneous aberrations of the immune system have been described in systemic lupus erythematosus (SLE). Since the function and the fate of the immune system cells are governed principally by the biochemical events that follow ligation of specialized cell-surface receptors, we will review in this article recent developments in our understanding of abnormalities in the biochemistry of signals generated either by the antigen-receptor complex or by systems of costimulatory cell-surface molecules, like the CD28/CTLA4:CD80/CD86 and the CD40:CD40L pairs found on the surface membrane of lupus immune cells.

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“…Furthermore, the CD28 sphingomyelin-ceramide signaling pathway, which overlaps with CD95 signaling, initiates induction of apoptosis via activation-induced cell death (AICD) [1]. These data suggest that in SLE patients, the reported overexpression of CD28 [2] is associated with low levels of CD28? T cells.…”

Section: Discussionmentioning

confidence: 95%

“…Binding to CD28 by the ligands CD80 and CD86 produces T-cell proliferation and cytokine secretion, and is furthermore associated with apoptosis inhibition [1]. Some studies have observed higher levels of CD28 in patients with SLE compared to healthy controls (HC) [2][3][4]; however, no studies have been performed on Latin-American populations in which specific organ damage has also been evaluated. Therefore, the aims of this study were to analyze CD28 serum levels in a group of SLE patients and HC to determine if CD28 serum levels were increased in a Mexican population, and to associate these levels with specific clinical manifestations of disease activity.…”

Section: Introductionmentioning

confidence: 97%

Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus

et al. 2010

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CD28 is one of the main activator receptors involved in systemic lupus erythematosus (SLE) pathogenesis, and its expression and serum levels are significantly higher in patients with SLE and other autoimmune diseases than in healthy controls (HC). However, it is unknown whether this increase is associated with specific organ damage. Therefore, our objective was to measure the CD28 levels in serum from SLE and HC groups to confirm the CD28 serum levels increase, as reported previously, and to determine whether this increase was associated with specific organ activity and the SLE Disease Activity Index (SLEDAI). Forty SLE patients and 40 matched HC were included, and the age, disease duration, SLEDAI and Mexican SLEDAI were recorded for the SLE group. CD28 serum levels were measured by ELISA. There was a statistically significant increase in the CD28 serum levels of SLE patients compared to controls (p = 0.039); however, we did not find any significant correlation with disease activity indices or organ involvement, although we found a significant but low correlation with C3. Our results and a review of the literature suggest that the increase in CD28 serum levels may be the result of CD28 gene overexpression, which could be related to the decrease in CD28+ T cells, T-cell hyporesponsiveness and immune impairment that occurs in SLE.

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Effect of CD28 Antibody on T Cells from Patients with Systemic Lupus Erythematosus

Cited by 19 publications

References 0 publications

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Immune cell signaling aberrations in human lupus

Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus

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