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.