Regulation of Th2 Responses and Allergic Inflammation through Bystander Activation of CD8+ T Lymphocytes in Early Life

Abstract

Th2-biased immune responses characterizing neonates may influence the later onset of allergic disease. The contribution of regulatory T cell populations in the prevention of Th2-driven pathologies in early life is poorly documented. We investigated the potential of CD8+ T cells stimulated at birth with alloantigens to modulate the development of allergic airway inflammation. Newborn mice were immunized with semiallogeneic splenocytes or dendritic cells (DCs) and exposed at the adult stage to OVA aeroallergens. DC-immunized animals displayed a strong Th1 and Tc1/Tc2 alloantigen-specific response and were protected against the development of the allergic reaction with reduced airway hyperresponsiveness, mucus production, eosinophilia, allergen-specific IgE and IgG1, and reduction of lung IL-4, IL-5, IL-10, and IL-13 mRNA levels. By contrast, splenocyte-immunized mice displayed a Th2 and a weak Tc2 alloantigen-specific response and were more sensitive to the development of the allergen-specific inflammation compared with mice unexposed at birth to alloantigens. DC-immunized animals displayed an important increase in the percentage of IFN-γ–producing CD8+CD44high, CD8+CD62Lhigh, and CD8+CD25+ subsets. Adoptive transfers of CD8+ T cells from semiallogeneic DC-immunized animals to adult β2m-deficient animals prevented the development of allergic response, in particular IgE, IL-4, and IL-13 mRNA production in an IFN-γ–dependent manner, whereas transfers of CD8+ T cells from semiallogeneic splenocyte-immunized mice intensified the lung IL-4 and IL-10 mRNA level and the allergen-specific IgE. These findings demonstrated that neonatal induction of regulatory CD8+ T cells was able to modulate key parameters of later allergic sensitization in a bystander manner, without recognition of MHC class I molecules.

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

“…Immune regulation by these CD8 + T cells was dependent on production of IFN-γ and direct contact with the effector CD4 + T cells. Similarly, rapid bystander production of IFN-γ by memory CD8 + CD44 hi CD62L hi T cells has been shown to inhibit the development of Th2-driven allergic airway inflammation (24).…”

p16INK4a deficiency promotes IL-4–induced polarization and inhibits proinflammatory signaling in macrophages

“…BM-derived dendritic cells (DCs) were prepared as described. 22 BMDMs were obtained from femoral and tibial BM suspensions, plated at 10 ϫ 10 6 cells in 10-cm plates and differentiated in BMDM medium (RPMI 1640 containing HEPES 25mM supplemented with 10% low endotoxin FBS, 15% L929-conditioned medium, 2mM L-glutamine, 1mM gentamycine). Stimulations and microarray analysis were carried out at day 8.…”

Alleviation of Dermatophagoides microceras-induced allergy by an immunomodulatory protein, FIP-fve, from Flammulina velutipes in mice

“…The allergen-induced airway hyper-responsiveness, mucus production, and allergen-specific IgE and IgG1 were reduced in DC-immunized mice. 19) Heparin showed the ability to protect mice from Der p attack. Serum Der p-specific IgE level was lower in heparin-treated groups.…”

“…18) Vaccination with Th1-directing adjuvants inhibited the development of allergen-induced Th2-type responses via activated CD4 + T cells. 19) Der m is one of the major allergens in central Taiwan, but it was rarely reported. FIP-fve has the ability of stimulating Th1 cytokine production.…”