Abstract
CD26, acting as a costimulator of T cell activation, plays an important role in the immune system. However, the role of CD26 in the differentiation of T cell subsets, especially of new paradigms of T cells, such as Th17 and Tregs, is not fully clarified. In the present study, the role of CD26 in T cell differentiation was investigated in vitro. CD26 expression was analyzed in the different subsets of human peripheral blood T lymphocytes after solid-phase immobilized specific anti-CD3 mAb stimulation. Here, the percentage of CD4+ cells significantly increased and most of these cells were coexpressed with CD26, suggesting a close correlation of CD26 expression with the proliferation of CD4+ cells. Subsequently, after immobilized anti-CD3 mAb stimulation, CD26 high-expressing cells (CD26high) were separated from CD26 low-expressing cells (CD26low) by magnetic cell sorting. We found that the percentages of cells secreting Th1 typical cytokines (IL-2, IFN-γ) and Th17 typical cytokines (IL-6, IL-17, and IL-22) or expressing Th17 typical biomarkers (IL-23R, CD161, and CD196) in the CD26high group were markedly higher than in those in the CD26low group. In addition, a coexpression of CD26 with IL-2, IFN-γ, IL-17, IL-22, and IL-23R in lymphocytes was demonstrated by fluorescence microscopy. These results provide direct evidence that the high expression of CD26 is accompanied by the differentiation of T lymphocytes into Th1 and Th17, indicating that CD26 plays a crucial role in regulating the immune response.
Highlights
CD26/Dipeptidyl peptidase IV Tregs (DPPIV) is a multifunctional integral type II transmembrane glycoprotein with a broad cell-surface distribution [1]
The activation of Human peripheral blood lymphocyte mAb (HPBL) was determined by the measurement of expression of different lymphocyte activation markers (CD69, CD25, CD71, and CD26)
In comparison to nonactivated control cells, the percentage of CD26+ HPBLs was significantly increased after stimulation by 85% (33 ± 8% vs. 61 ± 14% of total HPBLs, p < 0:001) (Figure 1(a)), while the percentages of CD69+ and CD71+ cells were 6-fold and 5-fold compared to control cells (54:29 ± 20:87% vs. 9:07 ± 7:28%, p < 0:01; 30:6 ± 14% vs. 5:8 ± 2:46%, p < 0:05), respectively, and the percentage of CD25+ HPBLs was 68% higher than the value in the control group (17:65 ± 6:58% vs. 10:49 ± 9:41%) (Figure 1(b))
Summary
CD26/DPPIV (dipeptidyl peptidase) is a multifunctional integral type II transmembrane glycoprotein with a broad cell-surface distribution [1]. 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 [4, 5]. Both Th1 and Th2 cells express CD26, Th1 cells express three- to sixfold more CD26 protein than Th2 cells [6]. Other studies have indicated that CD26 expression induced the cytokine production of Th1 cells, including IL-2, IFN-γ, IL-10, and IL-12 [7].
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