Antigen-Nonspecific Recruitment of Th2 Cells to the Lung as a Mechanism for Viral Infection-Induced Allergic Asthma

Abstract

Respiratory viral infections have been shown to trigger exacerbations of asthma; however, the mechanism by which viral Th1-type inflammation exacerbates an allergic Th2-type disease remains unclear. We have previously shown that although adoptively transferred Th2 cells are inefficiently recruited to the lung in response to Ag, cotransfer of Th1 cells can increase accumulation of Th2 cells. In this study, we show that respiratory viral infection increases recruitment of resting Th2 cells specific for OVA even in the absence of OVA challenge. These findings suggest that the mechanism by which Th1-type inflammation enhances allergy is via an effect on recruitment. To study the role of the antigenic specificity of Th1 cells in the enhancement of Th2 cell recruitment and to determine whether virus-induced recruitment of OVA-specific Th2 cells may involve Th1 cells specific to a different Ag, we tested whether hen egg lysozyme-specific Th1 cells could synergize with OVA-specific Th2 cells. Challenge of mice that had received adoptively transferred Th1 cells plus Th2 cells induced the expression of inflammatory chemokines in the lung and increased both recruitment and activation of Th2 cells, leading to eosinophil recruitment, even in the absence of challenge with the Th2 Ag. Interestingly, as IL-5 supports eosinophilia, culture of resting Th2 cells with fresh APC induced production of IL-5 in the absence of specific Ag. Thus, Ag-specific activation of Th1 cells enhances the recruitment potential of the lung leading to recruitment and activation of Th2 cells. This implies that circulating Th2 cells in allergic individuals could enter the lungs in response to infection or inflammation and become activated to trigger allergy.

Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections

“…Thus, nonspecific recruitment of pre-established memory T cells to the lung airways appears to be a general feature of inflammation of the lung. However, the underlying mechanism of recruitment remains to be elucidated, although emerging data indicate that monocyte chemoattractant protein 1, RANTES, monocyte IFN-␥-inducible protein, and cytokine-responsive gene 2 may play key roles (28,40,41). We are currently investigating the impact of inflammatory chemokine production on the nonspecific recruitment of memory CD8 ϩ T cells during heterologous infection.…”

“…Recent studies have shown that respiratory virus infections induce an increase in the numbers of heterologous memory CD8 ϩ T cells in the lung or lung airways (14,19,28). However, it was not clear whether this reflected local proliferation or recruitment of cells from other sites.…”

Adjuvant modulation of the cytokine balance in Mycobacterium tuberculosis subunit vaccines; immunity, pathology and protection

“…35,36 Paradoxically, Th2 cells clearly have the potential to migrate into lung tissue in the presence of a strong inflammatory signal, as suggested by the tendency for respiratory infections to exacerbate asthma. 37 With the recent discovery of a third T-cell subset (Th-17 cells) regulated by IL-23, which is of particular importance in the inflammatory response, there is clearly a need for further detailed studies on the signals that control the trafficking of T-cell subsets and their importance in the expression of vaccine-induced pulmonary immunity. 38 Our study demonstrates a profound influence of the Th1/Th2 balance on the developmental kinetics as well as on the structure and cellular composition of the granuloma during infection.…”

Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia

“…This signals cDCs to produce CCL28 and recruit eff ector Th2 cells. Because Th2 recruitment to the lung is antigen nonspecifi c, it is possible that this mechanism contributes in other ways to allow the innate immune system to infl uence the antiviral response ( 36 ). For example, regulatory T cells express CCR10 and may be another important target of CCL28 ( 37 ).…”