Expansion of different subpopulations of CD26^-/low T cells in allergic and non-allergic asthmatics

CD26 displays variable levels between effector (TH₁₇ ≫ TH₁ > TH₂ > Treg) and naïve/memory (memory > naïve) CD4⁺ T lymphocytes. Besides, IL-6/IL^-6R is associated with TH₁₇-differentiation and asthma severity. Allergic/atopic asthma (AA) is dominated by TH₂ responses, while TH₁₇ immunity might either modulate the TH₂-dependent inflammation in AA or be an important mechanism boosting non-allergic asthma (NAA). Therefore, in this work we have compared the expression of CD26 and CD126 (IL-6Rα) in lymphocytes from different groups of donors: allergic (AA) and non-allergic (NAA) asthma, rhinitis, and healthy subjects. For this purpose, flow cytometry, haematological/biochemical, and in vitro proliferation assays were performed. Our results show a strong CD26-CD126 correlation and an over-representation of CD26^- subsets with a highly-differentiated effector phenotype in AA (CD4⁺CD26^-/low T cells) and NAA (CD4^-CD26^- γδ-T cells). In addition, we found that circulating levels of CD26 (sCD26) were reduced in both AA and NAA, while loss of CD126 expression on different leukocytes correlated with higher disease severity. Finally, selective inhibition of CD26-mRNA translation led to enhanced T cell proliferation in vitro. These findings support that CD26 down-modulation could play a role in facilitating the expansion of highly-differentiated effector T cell subsets in asthma.