One of the strategies proposed to decrease Th2-type allergic disorders initiated early in life is based on the development of regulatory T cells. Aurore Dubois and her research team previously described that Th2-type skewed immune responses induced in newborn mice are controlled by IFN-gamma producing CD8⁺ T cells.
They investigated here the potential of CD8⁺ T cells stimulated at birth with alloantigens to modulate in a bystander manner the development of allergic asthma. BALB/c mice were immunized with (A/J x BALB/c) F1 spleen cells or bone marrow-derived dendritic cells and exposed at the adult stage to ovalbumin aeroallergens. Mice immunized at birth with F1 dendritic cells were protected against the development of an asthmatic reaction induced by exposure to ovalbumin. They displayed a reduction of the airway hyperresponsiveness, eosinophilic inflammation, allergen-specific IgE up-regulation and IL-4, IL-5 and IL-13 mRNA levels induction in the lung and the draining lymph nodes. In contrast, mice immunized with F1 spleen cells were more sensitive to the development of these asthmatic patterns against ovalbumin compared with mice unexposed to alloantigens. CD8⁺ T cells from mice immunized at birth with F1 spleen cells display a Tc2 profile characterized by the production of IL-5 and IL-13 whereas the ones isolated from mice injected with F1 dendritic cells display a Tc1/Tc2 profile with a predominance of IFN-gamma producing cells. Adoptive transfers of CD8⁺ T cells isolated from BALB/c mice immunized at birth with F1 dendritic cells in adult CD8⁺ T cells-compromised mice ( i.e. beta2-microglobulin-deficient mice) exposed to ovalbumin aeroallergens impair the IL-4, IL-10 and IL-13 mRNA production in the lung and the allergen-specific IgE up-regulation in contrast with CD8⁺ T cells isolated from BALB/c mice immunized with F1 spleen cells.
These findings demonstrate that Tc2 or Tc1/Tc2 regulatory CD8⁺ T cells able to modulate asthmatic pathologies in a bystander manner may be induced at birth.