Costimulation of CD4+ and CD8+ T cells through CD26: the ADA-binding epitope is not essential for complete signaling

• Published in: Journal of leukocyte biology Vol. 58; no. 3; pp. 325 - 330
• Main Authors: De Meester, I A, Kestens, L L, Vanham, G L, Vanhoof, G C, Vingerhoets, J H, Gigase, P L, Scharpé, S L
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.09.1995
• Subjects: Adenosine Deaminase - metabolism; AIDS/HIV; CD3 Complex - physiology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; cytokine profile; Dipeptidyl Peptidase 4 - immunology; dipeptidyl peptidase IV; Humans; In Vitro Techniques; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Interleukin-5 - biosynthesis; Lymphocyte Activation; memory T cells; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.58.3.325

It was previously shown that CD26 (DPP IV, EC 3.4.14.5) is a binding site for adenosine deaminase (ADA, EC 3.5.4.4) on T cells and that costimulation by some anti‐CD26 monoclonal antibodies (mAbs) and anti‐CD3 induces CD4+ T cell proliferation. The CD26 epitopes involved in costimulation, the precise sequence of the events preceding proliferation, and the response of CD8+ compared with CD4+ T cells to CD26 were not extensively studied. We therefore compared the effects of the novel TA5.9 anti‐CD26 mAb, recognizing an ADA‐binding epitope, and the clearly distinct anti‐Ta1 reference anti‐CD26 mAb for their costimulatory properties in various T cell subsets. Both purified CD4+ and CD8+ T cells proliferated upon costimulation with anti‐CD3 and either anti‐CD26 mAb, but anti‐TA5.9 mAb induced a more potent response than anti‐Tal. Either anti‐CD26 mAb, together with anti‐CD3, caused a similar sequential up‐regulation of CD69, CD25 (IL‐2Rα), and CD71 (transferrin receptor) expression on CD4+ and CD8+ T cells. The activation markers appeared faster on the CD45R0+ than on the CD45R0− subsets. After costimulation, CD4+ T cell cultures contained significant amounts of the Th1 cytokines EL‐2, interferon‐γ (IFN‐γ), and tumor necrosis factor‐α (TNF‐α). In CD8+ T cell cultures relatively more IFN‐γ and TNF‐α but almost no IL‐2 was measured after triggering of CD3 and CD26. Our data demonstrate that the recognition of the ADA‐binding epitope is not a prerequisite for the costimulatory capacity of anti‐CD26 mAbs. Both CD4+ and CD8+ T cells and their CD45R0−and CD45R0+ subsets are sensitive to various aspects of activation via CD26, but the magnitude and/or kinetics differ according to the anti‐CD26 used and the T cell subset studied.