Adenosine deaminase potentiates the generation of effector, memory, and regulatory CD4+ T cells.
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.
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Spain.
José M
JM
Martinez-Navio
Víctor
V
Casanova
Rodrigo
R
Pacheco
Isaac
I
Naval-Macabuhay
Núria
N
Climent
Felipe
F
Garcia
José M
JM
Gatell
Josefa
J
Mallol
Teresa
T
Gallart
Carme
C
Lluis
Rafael
R
Franco
D000243:Adenosine Deaminase / Q000378:metabolism*; D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D000243:Adenosine Deaminase