Vaccinations with T‐helper type 1 directing adjuvants have different suppressive effects on the development of allergen‐induced T‐helper type 2 responses

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.

Section: Discussionmentioning

confidence: 99%

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

Dubois

Deruytter

Adams

et al. 2010

“…Histological analyses were conducted as described previously (29). In brief, the lung tissues were fixed with formaldehyde and embedded in paraffin.…”

Section: Lung Histopathologymentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Homologs of Anisakis simplex Suppress Th2 Response in Allergic Airway Inflammation Model via CD4+CD25+Foxp3+ T Cell Recruitment

Park

Cho

Park

et al. 2009

“…Larvae migrate from the lungs to the small intestine, where they mature into egg-producing adults (2). In addition to the polarized Th2 immune response in the local lymphoid tissue of the gut, N. brasiliensis also induces a strongly polarized Th2 response in the lymph node draining the infection site (3), and in the lung (4). We have previously shown that intracutaneous inoculation of N. brasiliensis L3 in the ear induces a potent Th2 response in the local cervical lymph node (CLN), 4 and that larvae migrate normally to the lung and intestine, followed by a host-protective response resulting in rapid expulsion.…”

mentioning

confidence: 99%

Neutrophils Clear Bacteria Associated with Parasitic Nematodes Augmenting the Development of an Effective Th2-Type Response

Pesce

Liu

Hamed

et al. 2008

Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however, little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node was examined after N. brasiliensis inoculation. Pronounced increases of several chemokines, including CCL2, were observed. Compared with wild-type mice, elevations in a Gr-1bright population in the draining lymph node was significantly decreased in CCL2−/− mice after N. brasiliensis inoculation. Further flow cytometric and immunofluorescent analysis showed that in wild-type mice, Gr-1+ cells transiently entered and exited the draining lymph node shortly after N. brasiliensis inoculation. The Gr-1bright population was comprised of neutrophils expressing TGF-β and TNF-α. Following Gr-1+ cell depletion, N. brasiliensis infection resulted in transient, but significantly increased levels of IFN-γ, increased serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality, and delayed worm expulsion. Furthermore, bacteria were readily detected in vital organs. Infection of Gr-1+ cell-depleted mice with N. brasiliensis larvae that were pretreated with antibiotics prevented bacterial dissemination, Th1 inflammatory responses, and decreases in host survival. This study indicates that parasitic nematodes can be an important vector of potentially harmful bacteria, which is typically controlled by CCL2-dependent neutrophils that ensure the optimal development of Th2 immune responses and parasite resistance.