TY - JOUR
T1 - CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse
AU - Pacheco, R.
AU - Martinez-Navio, J. M.
AU - Lejeune, M.
AU - Climent, N.
AU - Oliva, H.
AU - Gatell, J. M.
AU - Gallart, T.
AU - Mallol, J.
AU - Lluis, C.
AU - Franco, R.
PY - 2005/7/5
Y1 - 2005/7/5
N2 - 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 EC50 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 ADA-anchoring 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-γ, TNF-α, and IL-6.
AB - 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 EC50 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 ADA-anchoring 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-γ, TNF-α, and IL-6.
KW - Adenosine deaminase
KW - Costimulation
KW - Immunosynapse
UR - http://www.scopus.com/inward/record.url?scp=22144486561&partnerID=8YFLogxK
U2 - 10.1073/pnas.0501050102
DO - 10.1073/pnas.0501050102
M3 - Article
C2 - 15983379
AN - SCOPUS:22144486561
SN - 0027-8424
VL - 102
SP - 9583
EP - 9588
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 27
ER -