Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand

Hünig, Thomas; Tiefenthaler, Georg; Büschenfelde, K H Meyer zum; Meuer, Stefan

doi:10.1038/326298a0

Cited by 238 publications

(105 citation statements)

References 16 publications

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“…Similarly, Hunig et al recently activated peripheral blood T cells with LFA-3+ sheep erythrocytes in concert with certain anti-CD2 antibodies (46). Finally, we and other investigators recently have shown that purified LFA-3 antigen plus the antLCD2 antibody 9-1 can directly activate peripheral T cells, and that purified LFA-3 antigen directly interacts with purified CD2 antigen (refs.…”

Section: Discussionsupporting

confidence: 61%

“…Similar to thymocyte binding to thymic epithelial cells (39), binding of cultured synovial cells to thymocytes was inhibited by antibodies against synovial cell LFA-3 antigens and T cell CD2 molecules (Figure 1). These observations are of particular interest since thymocytes are capable of being triggered to proliferation by CD2 molecules, and the CD2 pathway of thymocyte activation is thought to be important in driving T cell maturation (46,47). Other peripheral stromal microenvironments such as tonsil and skin have been implicated in promoting the terminal stages of T cell maturation (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

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Synovial microenvironment‐t cell interactions

Haynes

Grover

Whichard

et al. 1988

Arthritis & Rheumatism

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Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell‐T cell interactions in vitro, we established cultures of fibroblast‐like synovial cells, and used these cells in a synovial cell‐T cell binding assay. Using T cells at various stages of differentiation and activation, we found that human thymocytes and mitogen‐activated peripheral blood T cells bound to fibroblast‐like synovial cells, whereas fresh peripheral blood T cells did not. Moreover, activated T cells from inflammatory synovial tissue or from synovial fluid also bound to fibroblast‐like synovial cells cultured in vivo. Antibodies against certain epitopes of the T cell CD2 (35.1) and synovial cell lymphocyte function‐associated antigen‐3 (LFA‐3) (TS2/9) molecules inhibited synovial cell‐thymocyte binding. However, these same anti‐CD2 and anti‐LFA‐3 antibodies only partially inhibited synovial cell binding to activated normal peripheral blood T cells. Moreover, T cells from inflammatory synovium from rheumatoid arthritis and psoriatic arthritis patients also bound to synovial cells in vitro. These findings demonstrate that fibroblast‐like synovial cells are capable of binding to human T cells in vitro, and suggest that during the course of inflammatory synovitis, synovial fibroblast‐T cell interactions may occur in vivo.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Synovial microenvironment‐t cell interactions

Haynes

Grover

Whichard

et al. 1988

Arthritis & Rheumatism

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“…However, CD2 also displays part of it e¡ect through speci¢c signals conveyed by its cytoplamic tail, which can also be mobilized by speci¢c combination of mAb (Hunig et al 1987). CD2 signalling acts through regulation of di¡erent tyrosine kinases in the TCR^CD3 complex or independently of them.…”

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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“…In fact, a complex pattern of signalling can be delivered to the T cell via CD2, probably determined by the conformational changes imposed on this molecule . A ligand for CD2 has been identified on sheep erythrocyte surface as being a 42 kd protein, termed T1 lTS (Hunig et al, 1987). The human cell surface equivalent for T IITS is the LFA3 molecule, a glycoprotein of mol.…”

Section: Introductionmentioning

confidence: 99%