Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

TLDR

The mechanisms by which immune responses to nonpathogenic environmental antigens result in allergy or tolerance remain unknown, and allergen‑specific CD4⁺ T cells are extremely rare but can be isolated from peripheral blood by cytokine profiling. Tr1 cells suppress responses through IL‑10, TGF‑β secretion and surface expression of CTLA‑4 and PD‑1. In healthy individuals Tr1 cells dominate allergen‑specific responses, whereas allergic individuals exhibit a higher frequency of IL‑4‑secreting Th2 cells, and altering the Tr1/Th2 balance—by blocking Tr1 suppressive activity or increasing Th2 frequency—shifts allergen‑specific Th2 activation ex vivo, indicating that the Tr1/Th2 balance is decisive for allergy development or recovery.

Abstract

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.