Anti-CD2 antibodies induce T cell unresponsiveness in vivo.

Gückel, Brigitte; Berek, Claudia; Lutz, Martina S.; Altevogt, Peter; Schirrmacher, Volker; Kyewski, Bruno

doi:10.1084/jem.174.5.957

Cited by 86 publications

(54 citation statements)

References 53 publications

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“…In addition to providing costimulatory signals that promote T cell activation and B cell differentiation (23,24), signaling through CD2 has complex immunosuppressive effects both in vitro and in vivo (25,26,95,96). Treatment of mice with anti-CD2 prevents the onset of autoimmune diabetes mellitus and allergic experimental encephalomyelitis (97,98).…”

Section: Discussionmentioning

confidence: 99%

“…However, anti-CD2 monoclonal antibodies (MAb) also have inhibitory effects on T cell function both in vitro (25) and in vivo (26) 60 years), and the mean disease duration was 6 years (range 0-30 years). The study group included 6 hospitalized individuals with newly diagnosed, untreated SLE; the remainder were ambulatory and were receiving prednisone, nonsteroidal antiinflammatory drugs, or hydroxychloroquine, but not cytotoxic drugs.…”

Section: Decreased T Cell Response To Anti-cd2 In Systemic Lupus Erytmentioning

confidence: 99%

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Decreased T cell response to anti‐CD2 in systemic lupus erythematosus and reversal by anti‐CD28. Evidence for Impaired T Cell‐Accessory Cell Interaction

Horwitz

Tang

Stimmler

et al. 1997

Arthritis & Rheumatism

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Objective. To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect.Methods. Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti-CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb.Results. The proliferative response to anti-CD2 was decreased to a greater extent than was the response to anti-CD3 or PHA in SLE patients. This defect was found in approximately one-half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing. Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of a neutralizing antibody Submitted for publication June 10, 1996; accepted in revised form November 22, 1996. to interleukin-10, largely reversed the anti-CD2 proliferative defect. Significantly fewer CDS+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells.Conclusion. This study provides evidence that some functional T cell defects in SLE may be due, at least in part, to decreased CD28-mediated costimulatory activity following the interaction of T cells with conventional accessory cells.

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Section: Discussionmentioning

confidence: 99%

Section: Decreased T Cell Response To Anti-cd2 In Systemic Lupus Erytmentioning

confidence: 99%

Decreased T cell response to anti‐CD2 in systemic lupus erythematosus and reversal by anti‐CD28. Evidence for Impaired T Cell‐Accessory Cell Interaction

Horwitz

Tang

Stimmler

et al. 1997

Arthritis & Rheumatism

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“…As for mice lacking ICAM-1, the e¡ect is more pronounced when low-a¤nity binding peptides are used. The polyclonal T-cell hyporesponsiveness that persists long after membrane CD2 recovery follows incubation with antibodies suggests that some anti-CD2 mAbs also deliver an inhibitory signal (Guckel et al 1991). It is interesting to note that the blockade of CD2 and LFA-1 co-stimulation pathways could result in a T-cell anergy state mimicking that described following blockade of CD28 or B7 activation (Bell & Imboden 1995).…”

Section: Targeting Lfa-1 and Cd2 Molecules (A) Inhibition Of Lfa-1^icmentioning

confidence: 99%

Mechanisms of tolerance induction: blockade of co–stimulation

Sébille

Vanhove

Soulillou

2001

Phil. Trans. R. Soc. Lond. B

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Induction of tolerance to transplantation antigens is believed to be a promising way to achieve long-term allograft survival without a deleterious immunosuppressive regimen. T-cell activation, which is an essential feature of graft rejection, requires a ¢rst signal provided by T-cell receptor (TCR) ligation and a second signal provided by engagement of co-stimulatory molecules with their respective ligands on antigen-presenting cells. The coordinated triggering of these two independent signalling systems ensures the full T-cell activation, including proliferation and acquisition of e¡ector function. TCR occupancy in the absence of co-stimulatory signals leads to a sustained loss of antigen responsiveness called clonal anergy, which could be of major importance in transplantation. In vivo, co-stimulation blockade was indeed shown to allow for long-term allograft survival in several transplantation models. However, the current continuous identi¢cation of new co-stimulatory molecules suggests that a functional redundancy of the system exists and that tolerance to transplantation antigens might be achieved more easily through the combined blockade of two or several co-stimulatory signals.In this review, we analyse the biological e¡ects of the disruption of some co-stimulation pathways in vitro and in vivo and discuss their potential interest for tolerance induction.

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“…The cytoplasmic domain of CD5 has an immunoreceptor tyrosine-based inhibition motif (ITIM) and has been shown to negatively regulate signaling through both the TCR and BCR [27,29]. In vitro and in vivo studies with anti-CD2 antibodies revealed inhibition of T cell function, including longlasting hyporesponsiveness, that could not be entirely explained simply by blockade of CD2 interactions with its ligand [30,31]. Thus, both CD2 and CD5 appear capable of antagonizing T cell activation, whereas in contrast, CD28 has only been reported to augment mature T cell activation.…”

Section: Discussionmentioning

confidence: 99%

A novel role for CD28 in thymic selection: elimination of CD28/B7 interactions increases positive selection

2005

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While the importance of the CD28/B7 costimulation pathway is well established for mature T cells, the role of CD28 in thymocyte selection is less well defined. The role of CD28 in both negative and positive selection was assessed using H-Y-specific TCRtransgenic (Tg) RAG-2-deficient (H-Yrag) mice. Negative selection in male H-Yrag mice was not affected by deficiency in CD28 or B7. Surprisingly, absence of CD28 or B7 in HYrag females resulted in increased numbers of CD8 single-positive (SP) thymocytes. The CD8 SP thymocytes found in these females were mature and functionally competent. Furthermore, double-positive (DP) thymocytes from CD28-knockout (CD28KO) or B7.1/B7.2 double-KO (B7DKO) females had higher levels of both CD5 and TCR than those from WT females, consistent with a stronger selecting signal. CD28KO H-Yrag fetal thymic organ cultures also had elevated numbers of thymic CD8 SP cells, reflecting increased thymic differentiation and not recirculation of peripheral T cells. Finally, increased selection of mature CD4 and CD8 SP T cells was observed in non-TCR-Tg CD28KO and B7DKO mice, indicating that this function of CD28-B7 interaction is not unique to a TCR-Tg model. Together these findings demonstrate a novel negative regulatory role for CD28 in inhibiting differentiation of SP thymocytes, probably through inhibition of thymic selection.

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Anti-CD2 antibodies induce T cell unresponsiveness in vivo.

Cited by 86 publications

References 53 publications

Decreased T cell response to anti‐CD2 in systemic lupus erythematosus and reversal by anti‐CD28. Evidence for Impaired T Cell‐Accessory Cell Interaction

Decreased T cell response to anti‐CD2 in systemic lupus erythematosus and reversal by anti‐CD28. Evidence for Impaired T Cell‐Accessory Cell Interaction

Mechanisms of tolerance induction: blockade of co–stimulation

A novel role for CD28 in thymic selection: elimination of CD28/B7 interactions increases positive selection

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