Cd28 expression on t cell subsets in vivo and cd28‐mediated t cell response in vitro in patients with rheumatoid arthritis

Sfikakis, P.; Zografou, Amalia; Viglis, V; Iniotaki-Theodoraki, A; Piskontaki, Ifigenia; Tsokos, George C.; Sfikakis, P.P.; Choremi-Papadopoulou, H

doi:10.1002/art.1780380512

Cited by 30 publications

(20 citation statements)

References 15 publications

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“…In contrast, the expansion of CD28 Ϫ T cell subsets appears to be ligated to extraarticular sites of inflammation (32) and reflects a systemic antigen challenge, for example, persistent infection (58). Our findings parallel reports on CD8 ϩ T cells which show: (i) that CD8 ϩ CD28 high are enriched among the cells that migrate across endothelial monolayers (35) and (ii) that, in contrast to peripheral blood, RA synovial fluid T cells are almost exclusively CD28 ϩ (41), which lead us to independently suggest that CD28 high T cells may preferentially migrate to certain sites of inflammation (33,34,41).…”

supporting

confidence: 88%

“…In contrast, other studies of the PBL T cell proliferative response of active, untreated RA patients to TCR/CD3 ϩ CD28 costimulation show a similar response in RA patients and healthy controls (41). These previous studies did not, however, allow direct comparison of the proliferative capacity of T cells from active and inactive RA patients (28,29,41).…”

Section: Cd28 Levels In Cd4 T Cells From Ra Patients Correlate With Tmentioning

confidence: 81%

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Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis

Salazar-Fontana

Sanz

Mérida

et al. 2001

Clinical Immunology

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supporting

confidence: 88%

Section: Cd28 Levels In Cd4 T Cells From Ra Patients Correlate With Tmentioning

confidence: 81%

Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis

Salazar-Fontana

Sanz

Mérida

et al. 2001

Clinical Immunology

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“…Indeed, the expression of CD28 on CD8 + T cells shows dramatic individual variation in humans, ranging from 18% to 87% of peripheral blood CD8 + T cells (30). In human transplant recipients, heterogeneity in the responsiveness to conventional immunosuppression is well recognized but poorly understood (31).…”

Section: Discussionmentioning

confidence: 99%

Asialo GM1+ CD8+ T cells play a critical role in costimulation blockade–resistant allograft rejection

Trambley¹,

Bingaman²,

Lin³

et al. 1999

J. Clin. Invest.

332

295

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Simultaneous blockade of the CD40 and CD28 costimulatory pathways is an effective treatment strategy to promote allograft acceptance but does not lead to indefinite allograft survival. The immune mechanisms responsible for costimulation-independent rejection are not defined. Here we have studied the rejection responses of murine C57BL/6 recipients, which we show to be relatively resistant to inhibition by combined CD40/CD28 blockade. We demonstrate that asialo GM1 + CD8 + cells play a critical role in this costimulation blockade-resistant rejection. These results provide new insights into the costimulatory requirements for T-cell subsets and demonstrate for the first time that combined blockade of the CD40 and CD28 pathways does not adequately inhibit CD8-mediated skin allograft rejection. Furthermore, we provide evidence that asialo GM1 is a potentially important therapeutic target for CD8-dependent immune responses.

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“…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. Although we cannot completely eliminate this possibility, it is unlikely that the migration of CD28 T cells is a common reason for T cell lymphopenia in SLE, since the homing of T cells to the specific organs is not typical except for certain cases.…”

Section: Discussionmentioning

confidence: 99%

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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Cd28 expression on t cell subsets in vivo and cd28‐mediated t cell response in vitro in patients with rheumatoid arthritis

Cited by 30 publications

References 15 publications

Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis

Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis

Asialo GM1+ CD8+ T cells play a critical role in costimulation blockade–resistant allograft rejection

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

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