PD-1 expression on T cell subsets from peripheral blood of patients with allergic diseases

Abstract

Pathogenesis of allergic diseases is based on the activation of Th2 immune response. T cell response to antigens is known to be regulated by various co-stimulatory and inhibitory signals; inhibitory receptors include PD-1 and Tim-3 molecules. Interaction of the PD-1 receptor with its ligands leads to suppression of activation, proliferation of T cells and production of cytokines by these cells. In chronic bacterial and viral infections, increased expression of PD-1 and Tim-3 on T cells is a marker of cellular exhaustion, since the cytokine production is reduced in cells positive for these inhibitory receptors. Involvement of the co-inhibitory PD-1 receptor into pathogenesis of allergic diseases has not been sufficiently studied, and the data available from the current literature are scarce and contradictory. Therefore, the aim of our study was to evaluate the expression level of co-inhibitory PD-1 and Tim-3 receptors on CD4+ and CD8+T cells, as well as expression of PD-1 on allergen-specific Th2A cells in allergic bronchial asthma (BA) and allergic rhinitis (AR) beyond the pollination season. We used the flow cytometry method to assess immune phenotype of peripheral blood cells from blood donors and patients with allergic diseases, in order to evaluate expression of PD-1 and Tim- 3 markers. The study included 7 patients with allergic asthma, 10 patients with AR beyond the exacerbation phase, and 14 healthy, allergy-free individuals. It was found that the number of CD4+ and CD8+ cells expressing the PD-1 molecule in peripheral blood of patients with BA and AR was within the ranges of healthy individuals. A decrease in CD4+ cells expressing Tim-3 marker was observed only in the group of patients with AR which may be caused both by the absence of pollen allergens and remission of the disease. The content of allergen-specific Th2A cells (CD4+CD45RO+CD27-CRTh2+CD161+) in patients with AR and BA was increased relative to the control group, thus suggesting a pathogenetic significance of this cell population for allergic diseases. However, the level of PD-1 expression on Th2A cells, as well as on the main T cell subpopulations, was comparable to donor values. This finding may suggest that PD-1 may be considered not only a marker of exhaustion as shown for chronic viral infections. Moreover, it also may reflect the activation status of various T cell subpopulations, including allergen-specific Th2A cells in allergic conditions.