Introduction
CD26/DPPIV (Dipeptidyl peptidase) is a multifunctional integral type II transmembrane glycoprotein with a broad cell-surface distribution [1]. As serine proteases, DPPIV cleaves the dipeptides after proline or alanine at the penultimate position of the N-terminus of several bioactive peptides, and thereby modulates their activities in diverse biological processes [2]. Besides its enzyme activity, CD26 was also shown as a co-stimulator involved in T-cell activation and differentiation by its interaction with other cellular molecules, such as adenosine deaminase (ADA), receptor-type protein tyrosine phosphatase (CD45), CARMA1 and caveolin-1 [3, 4]. The expression of CD26 in T lymphocytes is differentially regulated during T cell development. As an activation marker of T cells, CD26 is mainly expressed on CD4+ T cells, and it is thought to be a marker of T helper type 1 cells [5, 6]. Although both Th1 and Th2 cells express CD26, Th1 cells express three- to six-fold more CD26 protein than Th2 cells [7]. Other studies have indicated that CD26 expression induced the cytokine production of Th1 cells, including IL-2, IFN-γ, IL-10, and IL-12 [8]. In vivo , CD26-deficiency decreased the production of IL-2 and IL-4, delayed the production of IFN-γ in sera of mice after pokeweed mitogen (PWM)-stimulation, and increased secretion of IL-4, IL-5, and IL-13 in bronchoalveolar lavage (BAL) after ovalbumin-induced airway inflammation [9, 10]. In recent years, a new major effector population of CD4+ T cells has been defined and designated as Th17 cells [11]. One of the Th17 signature cytokines is IL-17 which is a pro-inflammation factor. Besides of IL-17, Th17 cells can produce other pro-inflammatory cytokines, including IL-22, IL-26, and IFN-γ [12]. Recent studies have shown that Th17 cells express IL-23R, lectin-like receptor CD161 and chemokine receptor CCR6 (CD196) [13, 14]. It has been reported that human Th17 cells express also a high level of DPPIV/CD26 [15]. However, the role of CD26 in the differentiation of Th17 cells has not been clearly investigated. Besides Th17 cells, regulatory T cells (Tregs) are another subpopulation of T helper cell. Tregs modulate the immune activities through their immunosuppressive effect on other self-reactive T cells thereby contributing to the maintenance of immunologic self-tolerance [16]. Previous studies found that the majority of human Tregs strongly and constitutively express CD25 (CD25high), and a fork-head transcription factor (Foxp3) is required for the development and function of CD4+CD25+ regulatory T cells and regards as one of the specific markers of Tregs [16]. Recently we have demonstrated a delayed allogeneic skin graft rejection in CD26-deficient mice. During graft rejection, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26–/– mice than in those of CD26+/+ mice [17]. To further investigate the role of CD26 in the differentiation of Th17 subpopulations of T lymphocytes, in this work, the correlation of CD26 expression with the differentiation of subsets of lymphocytes after antigen stimulation was investigated in vitro . We demonstrated that CD26 is closely involved in regulating the differentiation and functions of Th1 and Th17 subpopulations of T lymphocytes.