CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse.
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 A(2B) adenosine receptors. The physiological role of these interactions is not well understood. Our results show that by a 3-fold reduction in the EC(50) 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-gamma, TNF-alpha, and IL-6.
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.
R
R
Pacheco
J M
JM
Martinez-Navio
M
M
Lejeune
N
N
Climent
H
H
Oliva
J M
JM
Gatell
T
T
Gallart
J
J
Mallol
C
C
Lluis
R
R
Franco
D000243:Adenosine Deaminase / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018613:Microscopy, Confocal; D018047:Receptors, Purinergic P1 / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase