Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen

To investigate the role of CD26 in the immune system, CD26 gene knockout mice with C57BL/6 background were used to study the immune response after stimulation with PWM. CD26–/– mice display an apparently normal phenotype. However, in their spleen lymphocyte population the percentage of CD4+ T cells is lower, and that of NK cells is higher, than that in CD26+/+ mice. In their peripheral blood, CD26–/– mice present a conspicuously decreased proportion of CD4+ NKT lymphocytes. In vitro, the PWM‐stimulated IL‐4 production was decreased by 60–80% in the supernatants of spleen lymphocytes of CD26–/– mice compared to that of CD26+/+ mice, whereas levels of IL‐10 and IFN‐γ were increased. No significant differences were found in the production of IL‐2, IL‐5, IL‐6 and IL‐13 between knockout and wild‐type mice. After immunization of mice with PWM in vivo, serum levels of total IgG, IgG1, IgG2a and IgE were markedly lower in CD26–/– mice than those in CD26+/+ mice, while no difference was found in IgM production. Further analysis of cytokine levels in vivo revealed a reduced IL‐4, IL‐2 and delayed IFN‐γ production in sera of CD26–/– mice upon immunization with PWM. These results indicate that CD26 contributes to the regulation of development, maturation and migration of CD4+ T, NK and NKT cells, cytokine secretion, T cell‐dependent antibody production and immunoglobulin isotype switching of B cells.