The HIV‐1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression

Blanco, Julià; Valenzuela, Alejandro; Herrera, Carolina; Lluı́s, Carmen; Hovanessian, Ara G.; Franco, Rafael

doi:10.1016/s0014-5793(00)01751-8

Cited by 33 publications

(28 citation statements)

References 41 publications

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“…To determine whether the costimulatory effect of ADA is due to the association between ADA and CD26 on the T cell surface in the immunological synapse, cocultures were performed in conditions at which the ADA-CD26 interaction was interfered by using the anti-CD26 mAb Ta5.9, which is directed against the ADA binding domain of CD26 (35,36). When T cells were preincubated with Ta5.9 before the coculture with ADA-treated DC, the costimulatory effect of ADA in T cell activation was abrogated (Fig.…”

Section: Resultsmentioning

confidence: 99%

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

Pacheco

Martinez-Navío

Lejeune

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

221

192

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Adenosine deaminase (ADA), a protein whose deficit leads to severe combined immunodeficiency, binds to the cell surface by means of either CD26, A 1 adenosine receptors, or A2B adenosine receptors. The physiological role of these interactions is not well understood. Our results show that by a 3-fold reduction in the EC 50 for the antigen, ADA potentiated T cell proliferation in autologous cocultures with antigen-pulsed immature or mature dendritic cells. Costimulation was not due to the enzymatic activity but to the interaction of ADA-CD26 complexes in T cells with an ADAanchoring protein in dendritic cells. From colocalization studies, it is deduced that ADA colocalizing with adenosine receptors on dendritic cells interact with CD26 expressed on lymphocytes. This costimulatory signal in the immunological synapse leads to a marked increase (3-to 34-fold) in the production of the T helper 1 and proimmflamatory cytokines IFN-␥, TNF-␣, and IL-6. adenosine deaminase ͉ costimulation ͉ immunosynapse A denosine deaminase (ADA; EC 3.5.4.4) an enzyme involved in purine metabolism, catalyzes the hydrolytic deamination of adenosine or 2Ј-deoxyadenosine to inosine or 2Ј-deoxyinosine and ammonia. Congenital defect of ADA causes severe combined immunodeficiency, which is characterized by the absence of functional T and B lymphocytes in affected individuals (1). For many years, ADA was considered to be cytosolic, but it has been found on the cell surface of many cell types; therefore, it can be considered an ectoenzyme. In addition, ecto-ADA has been proposed to have a catalytic-independent function as a costimulatory molecule in lymphocytes (2).So far, two types of surface anchoring proteins for ecto-ADA have been described. The first type, with only one member, is CD26, a multifunctional protein of 110 KDa strongly expressed on epithelial cells (kidney proximal tubules, intestine, and bile duct) and on several types of endothelial cells and fibroblasts and on leukocyte subsets (3-5). The second type of ecto-ADA-binding proteins includes the adenosine receptors (AR) A 1 (A 1 R) (6) and A 2B (A 2B R) (7). The association between ADA and CD26 on the T cell surface has been proposed to have a costimulatory function during T cell antigen receptor-CD3 complex engagement (2). Because CD26 has a short cytoplasmatic tail, it needs partners to transduce the signal. Ishii et al. (8) have described that CD26-mediated signaling occurs through its association with CD45RO. At present, it is not known whether ADA generates a signal when it binds to AR. However, we have previously demonstrated that ADA binding to A 1 R or A 2B R is required for high efficiency affinity binding of the agonist and for efficient agonist-dependent signaling (6, 7).Dendritic cells (DC) are the most potent antigen-presenting cells (APC) specialized in the initiation of immune responses by directing the activation and differentiation of naïve T lymphocytes (9, 10). Immature DC (iDC) reside in most tissues to uptake antigen; they are engaged when exposed to danger ...

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Section: Resultsmentioning

confidence: 99%

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

Pacheco

Martinez-Navío

Lejeune

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

221

192

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“…17 By acting as a bridge between A 2B adenosine receptors on dendritic cells (DCs) surface and CD26 on T-cells surface, ADA acts as a costimulatory molecule in cocultures of SEA-presenting DCs and autologous T cells, not only enhancing T-cell proliferation, Th-1/pro-inflammatory cytokine secretion, 17 and naïve T-CD4 + cell activation, memory, and FOXP3 + generation, 18 but also increasing DCs immunogenicity in both healthy and HIVinfected subjects. 63 Although HIV gp120 envelope protein disrupts ADA-CD26 interaction, 64 possibly contributing to the HIV-promoted immunodeficiency, 19 ADA is still able to enhance autologous T-cell proliferation against inactivated-HIV presentation by DC in individuals under cART (Fig. 3), 16 suggesting a beneficial role for ADA on improving HIV-specific T-cell responses in those individuals.…”

Section: Adjuvants To Favor or Impair Antigen Presentationmentioning

confidence: 99%

Dendritic cell based vaccines for HIV infection

García

Plana

Climent

et al. 2013

Human Vaccines & Immunotherapeutics

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“…The HIV envelope is believed to be a major player in the HIV-mediated killing of uninfected CD4 T cells. Envelope-induced apoptosis occurs as a result of an infected cell's interaction with an uninfected cell CD4 receptor (1,23,40) and/or the CXCR4/CCR5 coreceptor (11,13,14,45). Infected macrophages can also contribute to the depletion of uninfected T lymphocytes by inducing apoptosis in both CD4 ϩ and CD8 ϩ cells (6,8).…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Modulates HIV-1 Envelope-Induced Bystander Apoptosis through gp41

Wang

Nadeau

et al. 2010

J Virol

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Human immunodeficiency virus (HIV) envelope (Env)-mediated bystander apoptosis is known to cause the progressive, severe, and irreversible loss of CD4 ؉ T cells in HIV-1-infected patients. Env-induced bystander apoptosis has been shown to be gp41 dependent and related to the membrane hemifusion between envelopeexpressing cells and target cells. Caveolin-1 (Cav-1), the scaffold protein of specific membrane lipid rafts called caveolae, has been reported to interact with gp41. However, the underlying pathological or physiological meaning of this robust interaction remains unclear. In this report, we examine the interaction of cellular Cav-1 and HIV gp41 within the lipid rafts and show that Cav-1 modulates Env-induced bystander apoptosis through interactions with gp41 in SupT1 cells and CD4 ؉ T lymphocytes isolated from human peripheral blood. Cav-1 significantly suppressed Env-induced membrane hemifusion and caspase-3 activation and augmented Hsp70 upregulation. Moreover, a peptide containing the Cav-1 scaffold domain sequence markedly inhibited bystander apoptosis and apoptotic signal pathways. Our studies shed new light on the potential role of Cav-1 in limiting HIV pathogenesis and the development of a novel therapeutic strategy in treating HIV-1-infected patients.

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The HIV‐1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression

Cited by 33 publications

References 41 publications

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse

Dendritic cell based vaccines for HIV infection

Caveolin-1 Modulates HIV-1 Envelope-Induced Bystander Apoptosis through gp41

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