Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells

Akdis M., Verhagen J., Taylor A., Karamloo F., Karagiannidis C., Crameri R., ...Daha Fazla

JOURNAL OF EXPERIMENTAL MEDICINE, cilt.199, sa.11, ss.1567-1575, 2004 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 199 Sayı: 11
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1084/jem.20032058
  • Dergi Adı: JOURNAL OF EXPERIMENTAL MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1567-1575
  • Anahtar Kelimeler: peripheral tolerance, allergens, suppression, interleukins, immune regulation, CD8(+) T-CELLS, NONALLERGIC INDIVIDUALS, IN-VITRO, TOLERANCE, CD4(+), INTERLEUKIN-10, ACTIVATION, EXPRESSION
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.