Adenosine deaminase enhances T-cell response elicited by dendritic cells loaded with inactivated HIV.
As host immunological defenses are impaired during HIV infection, it is difficult to elicit good responses when attempting to develop therapeutic vaccines against HIV. To try to solve this situation, adjuvants, particularly cytokines, are currently under evaluation. Owing to the fact that adenosine deaminase (ADA) is a member of the family of growth factor with deaminase activity, we tested whether it could improve immune responses in the development of HIV dendritic-cell-based therapeutic vaccines. A co-culture model approach has been used to test the usefulness of ADA as adjuvant. Monocyte-derived dendritic cells from HIV-infected patients were pulsed with inactivated HIV, matured and co-cultured with autologous T cells. Addition of ADA to the co-cultures resulted in enhanced CD4(+) and CD8(+) T-cell proliferation and robust ADA-induced increase in cytokine production (IFN-gamma, TNF-alpha and IL-6). As IFN-gamma, TNF-alpha and IL-6 promote the Th1 versus Th2 phenotype and improve T helper proliferation responses and antigen-specific CTL responses ADA may be considered a promising candidate for therapeutic vaccine adjuvant.
Climent
Núria
N
Hospital Clínic, Barcelona, Spain.
Martinez-Navio
José M
JM
Gil
Cristina
C
Garcia
Felipe
F
Rovira
Cristina
C
Hurtado
Carmen
C
Miralles
Laia
L
Gatell
José M
JM
Gallart
Teresa
T
Mallol
Josefa
J
Lluis
Carme
C
Franco
Rafael
R
D000243:Adenosine Deaminase / Q000378:metabolism*; D000328:Adult; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D038301:Virus Inactivation
D016207:Cytokines; D000243:Adenosine Deaminase