OX40 (CD134) controls memory T helper 2 cells that drive lung inflammation

Area of Science:

• Immunology
• Allergy and Asthma Research
• T cell Biology

Background:

• Asthma pathogenesis involves persistent memory Th2 cells.
• Mechanisms regulating established memory Th2 cells are poorly understood.
• The role of costimulatory molecules in memory Th2 cell function requires further investigation.

Purpose of the Study:

• To investigate the role of the costimulatory molecule OX40 in regulating memory Th2 cells.
• To determine if OX40 signaling is essential for recall responses in an asthma model.
• To elucidate the impact of OX40-OX40L interactions on allergic airway inflammation.

Main Methods:

• Expression analysis of OX40 on memory CD4+ T cells.
• In vivo blockade of OX40-OX40L interactions in sensitized animals during antigen rechallenge.
• Assessment of immune cell accumulation, airway hyperreactivity, mucus production, and Th2 cytokine levels.
• Analysis of T cell proliferation and survival in OX40-deficient mice upon antigen rechallenge.

Main Results:

• OX40 is expressed on memory CD4+ T cells.
• Blocking OX40-OX40L interactions suppressed effector cell accumulation in lymphoid tissues and lungs.
• Inhibition of OX40-OX40L signaling prevented key asthma features, including eosinophilia, airway hyperreactivity, and mucus secretion.
• OX40-deficient T cells exhibited impaired survival and accumulation after antigen rechallenge, indicating a critical role in recall responses.

Conclusions:

• OX40-OX40L interactions are essential regulators of memory Th2 cell function.
• Targeting OX40 signaling may represent a therapeutic strategy for managing allergic asthma.
• These findings underscore the importance of OX40 in maintaining the effector function of memory Th2 cells during recall responses.