Innate responsiveness of CD8 memory T-cell populations nonspecifically inhibits allergic sensitization.
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 T(H)1 immunity, and inhibit allergic sensitization and airway inflammation/hyperresponsiveness in a non-antigen-specific fashion.


CONCLUSIONS
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 T(H)1 over T(H)2 immunity and prevents allergic sensitization after exposure to environmental antigens or infection.
Leggat
Jamie A
JA
Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, United Kingdom.
Gibbons
Deena L
DL
Haque
Syeda F Y
SF
Smith
Adrian L
AL
Wells
James W
JW
Choy
Katherine
K
Lloyd
Clare M
CM
Hayday
Adrian C
AC
Noble
Alistair
A
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D033661:Oocysts / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000953:Antigens, Protozoan