CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-helper cell differentiation after inhaled allergen

Am J Respir Cell Mol Biol. 2001 May;24(5):563-8. doi: 10.1165/ajrcmb.24.5.4375.

Abstract

Airway inflammation after inhaled allergen exposure requires the recruitment, activation, and differentiation of antigen-specific T cells into T helper (Th) 2 effector cells. These processes are regulated not only by antigen engagement of the T-cell receptor, but also by specific accessory molecules on the surface of the T cell. We examined how the balance of signals derived through the CD28 and cytotoxic T-lymphocyte antigen (CTLA) 4 receptors modulate the outcome of inhaled antigen exposure in a murine model of allergic airway inflammation. Mice deficient in CD28 have defective Th2 cell development and failed to develop inflammation after sensitization and inhaled challenge with ovalbumin. Prevention of B7-CTLA4 interactions in CD28-deficient mice restored lymphocyte but not eosinophil recruitment to the airway. Analysis of cytokine gene expression revealed that T cells from CD28-deficient mice failed to differentiate into Th2 cells in either the presence or absence of B7-dependent signals, and therefore did not recruit eosinophils to the airway. Thus, the processes of T-cell recruitment to the airway and T-cell differentiation have distinct requirements for signals mediated through the CD28 and CTLA4 receptors, demonstrating that these receptors are important regulatory components in the development of allergic airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Administration, Inhalation
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Animals
  • Antibodies / pharmacology
  • Antigens, CD / metabolism
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • CD28 Antigens / genetics
  • CD28 Antigens / metabolism*
  • CTLA-4 Antigen
  • Cell Differentiation / immunology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eosinophils / immunology
  • Immunoconjugates*
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Pneumonia / complications
  • Pneumonia / immunology
  • Pneumonia / metabolism*
  • RNA, Messenger / metabolism
  • Respiratory Hypersensitivity / complications
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • Th2 Cells / immunology

Substances

  • Allergens
  • Antibodies
  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • Cytokines
  • Immunoconjugates
  • Membrane Glycoproteins
  • RNA, Messenger
  • Abatacept
  • Ovalbumin