Geisel School of Medicine
ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of ADA are implicated in the enhancement of CD80, CD83, CD86, CD40 and CCR7 expression on immature dendritic cells from healthy and HIV-infected individuals. These ADA- mediated increases in CD83 and costimulatory molecule expression is concomitant to an enhanced IL-12, IL-6, TNF-a, CXCL8(IL-8), CCL3(MIP1-a), CCL4(MIP-1b) and CCL5(RANTES) cytokine/chemokine secretion both in healthy and HIV-infected individuals and to an altered apoptotic death in cells from HIV-infected individuals. Consistently, ADA-mediated actions on iDCs are able to enhance allogeneic CD4 and CD8-T-cell proliferation, globally yielding increased iDC immunogenicity. Taken together, these findings suggest that ADA would promote enhanced and correctly polarized T-cell responses in strategies targeting asymptomatic HIV-infected individuals.
Casanova V, Naval-Macabuhay I, Massanella M, Rodríguez-García M, Blanco J, Gatell JM, García F, Gallart T, Lluis C, Mallol J, Franco R, Climent N, McCormick PJ. Adenosine deaminase enhances the immunogenicity of human dendritic cells from healthy and HIV-infected individuals. PLoS One. 2012;7(12):e51287. doi: 10.1371/journal.pone.0051287. Epub 2012 Dec 11. PMID: 23240012; PMCID: PMC3519778.
Dartmouth Digital Commons Citation
Casanova, Víctor; Naval-Macabuhay, Isaac Isaac; Massanella, Marta; and Rodríguez-García, Marta, "Adenosine Deaminase Enhances the Immunogenicity of Human Dendritic Cells from Healthy and HIV-Infected Individuals" (2012). Dartmouth Scholarship. 2524.