Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 8; pp. E784 - E793
• Main Authors: Mackenzie, Karen J, Nowakowska, Dominika J, Leech, Melanie D, McFarlane, Amanda J, Wilson, Claire, Fitch, Paul M, O'Connor, Richard A, Howie, Sarah E M, Schwarze, Jürgen, Anderton, Stephen M
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.02.2014; National Acad Sciences
• Series: PNAS Plus
• Subjects: Allergies; Animals; Biological Sciences; Bronchoalveolar Lavage; Cells; Cellular biology; Flow Cytometry; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Hypersensitivity - pathology; Immunologic Memory - immunology; Immunotherapy; Immunotherapy - methods; L-Selectin - immunology; Lung - pathology; Memory; Mice; Mice, Transgenic; Ovalbumin - immunology; Ovalbumin - therapeutic use; Peptide Fragments - immunology; Peptide Fragments - therapeutic use; Peptides; PNAS Plus; Th2 Cells - cytology; Th2 Cells - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1316178111

Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergen-experienced T cells. CD62L expression by allergen-experienced T cells corresponds to effector/effector memory (CD62L ˡᵒ) and central memory (CD62L ʰⁱ) subsets, which vary with allergen exposure (e.g., during, or out with, pollen season). The efficacy of PIT on different T helper 2 (Th2) cell memory populations is unknown. We developed a murine model of PIT in allergic airway inflammation (AAI) driven by adoptively transferred, traceable ovalbumin-experienced Th2 cells. PIT effectively suppressed AAI driven by unfractionated Th2 cells. Selective transfer of CD62L ʰⁱ and CD62L ˡᵒ Th2 cells revealed that these two populations behaved differently from one another and from previously characterized (early deletional) responses of naive CD4 ⁺ T cells to PIT. Most notably, allergen-reactive CD62L ˡᵒ Th2 cells were long-lived within the lung after PIT, before allergen challenge, in contrast to CD62L ʰⁱ Th2 cells. Despite this, PIT was most potent against CD62L ˡᵒ Th2 cells in protecting from AAI, impairing their ability to produce Th2 cytokines, whereas this capacity was heightened in PIT-treated CD62L ʰⁱ Th2 cells. We conclude that Th2 cells do not undergo an early deletional form of tolerance after PIT. Moreover, memory Th2 subsets respond differently to PIT. These findings have implications for the clinical translation of PIT in different allergic scenarios.