CD8+ T cell responses in allergic airway disease

Many studies have implied that CD8+ T cells play an important role in asthmatic responses by responding to allergen. This occurs when exogenous antigens are presented on MHCI molecules, and thus elicit CD8+ T cell responses. CD8+ T cells can, in the absence of viral infection, respond to allergens by producing type 2 cytokines such as IL-4 and IL-13. Through these cytokines, CD8+ T cells can participate in the pathology of asthmatic responses leading to airway hyperreactivity and eosinophil recruitment. Since increased CD8+ T cells are associated with increased asthma severity in humans post viral infection, we also wanted to determine the affect of a respiratory viral infection on the allergic airway response of mice sensitized to allergen. We hypothesized that viral infection would worsen the allergic response. We found that mice infected with respiratory syncytial virus (RSV) had increased numbers of CD8 + T cells in the BAL, and in allergen sensitized mice this correlated with increased airway hyperreactivity and type 2 cytokines in the lung. We also found an increase in the two CCR1 ligands, CCL3 and CCL5, during RSV infection over levels observed in allergen sensitized mice alone. Infection of allergen sensitized CCR1-/- mice with RSV did not result in an increase in the airway response. This was correlated with decreased levels of IL-13 and decreased numbers of CD4+ and CD8 + T cells in CCR1-/- mice when compared to wild type RSV infected CRA sensitized mice. Further analysis of T cell populations revealed that CD8+ T cells from CCR1-/- mice do not proliferate as well as wild type CD8+ T cells in vivo, although there was no difference in CD4+ T cell proliferation. This latter observation appeared to be related to their ability to migrate to lung draining lymph nodes. Additionally, CD8+ T cells from the lymph nodes of CCR1-/- mice did not produce IL-13 in response to allergen. Together, these studies suggest that viral infection can exacerbate asthmatic responses in part by increased recruitment of allergen responsive CD8+ T cells to the lungs of virally infected, allergen sensitized mice, and that this mechanism is partially dependent on CCR1.