Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells

Abstract

By interacting with CD26 on the CD4+ T cell surface and with the AdoR A(₂B) on the DC surface, ADA triggers a costimulatory signal for human T cells. The aim of this study was to know whether ADA-mediated costimulation plays a role in the differentiation of T cells. The results show that irrespective of its enzymatic activity and dependent on TNF-α, IFN-γ, and IL-6 action, ADA enhanced the differentiation of CD4+CD45RA+CD45RO⁻ naïve T cells toward CD4+CD25+CD45RO+ Teffs and CD4+CD45RA⁻CD45RO+ memory T cells. Furthermore, ADA potentiated generation of CD4+CD25(high)Foxp3+ Tregs by a mechanism that seems to be mainly dependent on the enzymatic activity of ADA. Interestingly, an ADA-mediated increase on Teff, memory T cell, and Treg generation occurred, not only in cocultures from healthy individuals but also from HIV-infected patients. These data suggest that ADA is a relevant modulator of CD4+ T cell differentiation, even in cells from immunologically compromised individuals.

Dendritic cell based vaccines for HIV infection

“…We have reported that ADA enhances T helper type 1 (Th1) and proinflammatory cytokine secretion in SEApulsed dendritic cells with autologous lymphocyte cocultures and CD3-triggered T cells. 17,18 and that the HIV envelope glycoprotein gp120 markedly reduces this effect. 19 These results could help to explain, at least in part, the progressive impairment of the immune system in HIV-infected patients.…”

“…Extracellular ADA mediates extracellular adenosine degradation and acts as a costimulatory molecule in T-cell activation processes. 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.…”

Adenosine Levels in Serum and Adenosine Deaminase Activity in Blood Cells of Dogs Infected byRangelia vitalii

“…In these diseases, the enzymatic activity was related to anemia, homeostasis, neurological disorders, and especially to the inflammatory response. Inflammation and immune responses can be modulated by various systems, including the purinergic system, in which adenosine plays an important role, and its effect as an anti-inflammatory molecule is already established in mammals (Martinez-Navio et al, 2001;Ye and Rajendran, 2009). The control of extracellular levels of adenosine is performed by E-ADA, an enzyme that presents 2 isoforms classified as E-ADA 1 and E-ADA 2 (Sharoyan et al, 2006).…”

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study

“…Interestingly, CD26 can increase T cell activation by increasing the co-stimulator CD86 on antigen-presenting cells in a process that requires enzymatic activity [10]. CD26 associates with other membrane proteins on T cells, including the tyrosine phosphatase CD45 and the ectoenzyme adenosine deaminase (ADA), which might be important for the co-stimulatory activity of CD26 [8,11]. However, inhibition of DPP-4 enzymatic activity may not block all these immune activities; the ability of soluble CD26 to bind ADA and enhancement of T cell proliferation can usually occur even when the active site of DPP-4 has been mutated [12,13].…”