Innate responsiveness of CD8 memory T-cell populations nonspecifically inhibits allergic sensitization

• Published in: Journal of allergy and clinical immunology 2008-11, Vol.122 (5), p.1014-1021.e4
• Main Authors: Leggat, Jamie A., PhD, Gibbons, Deena L., PhD, Haque, Syeda F.Y., BSc, Smith, Adrian L., PhD, Wells, James W., PhD, Choy, Katherine, BVSc, Lloyd, Clare M., PhD, Hayday, Adrian C., PhD, Noble, Alistair, PhD
• Format: Article
• Language: English
• Subjects: allergy; Allergy and Immunology; Animals; Antigens, Protozoan - immunology; Asthma - immunology; Biological and medical sciences; CD8 T cell; CD8-Positive T-Lymphocytes - immunology; Cell division; dendritic cell; Disease; Disease Models, Animal; Experiments; Flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hypersensitivity - immunology; IL-12; Immune system; Immunity, Innate; immunologic memory; Infections; Infections - immunology; innate immunity; Liver; Lymphocytes; Medical sciences; Mice; Mice, Inbred C57BL; Oocysts - immunology; Peptides; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Spleen; T cell receptors; T H1/T H2; Th1 Cells - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2008.08.011

Background Infection or stimulation of the innate immune system by nonspecific microbial antigens is thought to educate the immune system to respond appropriately to allergens, preventing allergy. Objective To determine the immunologic pathways that might explain how infection/microbial exposure inhibits allergic sensitization. Methods Immunologic studies of non–antigen-specific functions of CD8 memory cells, their maturation in vivo , and their effects in a mouse asthma model, to test the hypothesis that CD8 memory is shaped by innate immunity in a way that can inhibit allergic disease. Results We found that CD8 memory T-cell (CD8 Tm) populations bridge innate and adaptive immunity by responding to either antigen or cytokines alone. CD8 Tm populations partially subvert the clonal selection process by activating their neighbors through induction of dendritic cell IL-12. Stimulation of innate or acquired immunity in the lung or gut causes expansion/maturation of CD8 Tm populations, which provide an early source of cytokines, enhance TH 1 immunity, and inhibit allergic sensitization and airway inflammation/hyperresponsiveness in a non–antigen-specific fashion. Conclusion CD8 T-cell–mediated immune memory is long-lived and can retain its capacity for rapid cytokine release in a nonantigen-specific fashion. This novel type of memory enhances TH 1 over TH 2 immunity and prevents allergic sensitization after exposure to environmental antigens or infection.