T Cell Exhaustion in Allergic Diseases and Allergen Immunotherapy: A Novel Biomarker?

被引：0
作者：
Xu, Qingxiu [1 ]
Li, Le [1 ]
Zhu, Rongfei [1 ,2 ]
机构：
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Allergy, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Hosp, Inst Allergy & Clin Immunol, Tongji Med Coll, Wuhan 430030, Peoples R China
来源：
CURRENT ALLERGY AND ASTHMA REPORTS | 2025年 / 25卷 / 01期
关键词：
T cell exhaustion; Effector function; Inhibitory receptor; Allergic disease; Allergen immunotherapy; IMMUNE-RESPONSES; CHRONIC INFECTION; PD-1; EXPRESSION; LYMPHOCYTE ATTENUATOR; INHIBITORY RECEPTORS; EPIGENETIC LANDSCAPE; CD4(+); BLOCKADE; DIFFERENTIATION; PERSISTENCE;
D O I：
10.1007/s11882-025-01199-5
中图分类号：
R392 [医学免疫学];
学科分类号：
100102 ;
摘要：
Purpose of ReviewThis review explores the emerging role of T cell exhaustion in allergic diseases and allergen immunotherapy (AIT). It aims to synthesize current knowledge on the mechanisms of T cell exhaustion, evaluate its potential involvement in allergic inflammation, and assess its implications as a novel biomarker for predicting and monitoring AIT efficacy.Recent FindingsRecent studies highlight that T cell exhaustion, characterized by co-expression of inhibitory receptors (e.g., PD-1, CTLA-4, TIM-3), diminished cytokine production, and altered transcriptional profiles, may suppress type 2 inflammation in allergic diseases. In allergic asthma, exhausted CD4 + T cells exhibit upregulated inhibitory receptors, correlating with reduced IgE levels and airway hyperreactivity. During AIT, prolonged high-dose allergen exposure drives allergen-specific Th2 and T follicular helper (Tfh) cell exhaustion, potentially contributing to immune tolerance. Notably, clinical improvements in AIT correlate with depletion of allergen-specific Th2 cells and persistent expression of exhaustion markers (e.g., PD-1, CTLA-4) during maintenance phases. Blockade of inhibitory receptors (e.g., PD-1) enhances T cell activation, underscoring their dual regulatory role in allergy.SummaryT cell exhaustion represents a double-edged sword in allergy: it may dampen pathological inflammation in allergic diseases while serving as a mechanism for AIT-induced tolerance. The co-expression of inhibitory receptors on allergen-specific T cells emerges as a promising biomarker for AIT efficacy. Future research should clarify the transcriptional and metabolic drivers of exhaustion in allergy, validate its role across diverse allergic conditions, and optimize strategies to harness T cell exhaustion for durable immune tolerance. These insights could revolutionize therapeutic approaches and biomarker development in allergy management.
引用
收藏
页数：14
相关论文
共 173 条
  • [1] Blank C.U., Haining W.N., Held W., Et al., Defining 'T cell exhaustion, Nat Rev Immunol, 19, 11, pp. 665-674, (2019)
  • [2] Gallimore A., Glithero A., Godkin A., Et al., Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes, J Exp Med, 187, 9, pp. 1383-1393, (1998)
  • [3] Bowen D.G., Walker C.M., Adaptive immune responses in acute and chronic hepatitis C virus infection, Nature, 436, 7053, pp. 946-952, (2005)
  • [4] Angelosanto J.M., Blackburn S.D., Crawford A., Et al., Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection, J Virol, 86, 15, pp. 8161-8170, (2012)
  • [5] Pauken K.E., Wherry E.J., Overcoming T cell exhaustion in infection and cancer, Trends Immunol, 36, 4, pp. 265-276, (2015)
  • [6] Chow A., Perica K., Klebanoff C.A., Et al., Clinical implications of T cell exhaustion for cancer immunotherapy, Nat Rev Clin Oncol, 19, 12, pp. 775-790, (2022)
  • [7] McKinney E.F., Lee J.C., Jayne D.R., Et al., T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection, Nature, 523, 7562, pp. 612-616, (2015)
  • [8] Pawelec G., Is there a positive side to T cell exhaustion?, Front Immunol, 29, 10, (2019)
  • [9] Savoure M., Bousquet J., Jaakkola J.J.K., Et al., Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution, Clin Transl Allergy, 12, 3, (2022)
  • [10] Roberts G., Pfaar O., Akdis C.A., Et al., EAACI Guidelines on allergen immunotherapy: Allergic rhinoconjunctivitis, Allergy, 73, 4, pp. 765-798, (2018)
12345678910