The role of T cells in pulmonary resistance to Streptococcus pneumoniae

Abstract

As a result of the use of the pneumococcal capsular polysaccharide conjugate vaccine, there has been a decrease in the incidence of invasive pneumococcal disease (IPD) in young children and reduced rates of disease in adults through herd immunity. However, immunocompromised individuals are still at high risk for developing IPD and non-vaccine serotype (ST) replacement is an ongoing concern. Hence, there is a significant need to probe aspects of the immune response that could bear upon vaccine efficacy. CD4+T cells are necessary for protection against colonization, but little is known about the role of T cells in the innate response of pulmonary infection. The goal of this thesis is to assess the role of CD4+ and CD8 +T cells during innate immunity in resistance to Streptococcus pneumoniae.;Our results showed that infection with ST3, but not other STs, was significantly more lethal in CD84-/- mice than Wt or MHCII-/- mice. Lung CFUs were comparable, but blood CFUs were significantly higher in CD84-/- mice than Wt or MHCII-/- mice. Histopathological evaluation revealed marked inflammation in lung sections from CD8-/- mice, whereas those of Wt mice exhibited little inflammation. Studies of adoptive transfer and antibody depletion suggest that CD8+ T cells are responsible for protection against ST3.;Perform (Pfn)-/- and IFN-gamma-/- mice, which were used to discriminate between CD8 cell effector function and IFN-gamma secretion, had similar survival and inflammatory phenotypes to those of CD8 -/- mice. There were higher levels of neutrophils and neutrophil recruitment chemokines in IFN-gamma-/- and CD8-/- mice than in Wt mice. CD8-/-, IFN-gamma-/- and Pfn-/- mice also had higher levels of CD4+IL-17 + T (Th17) cells, suggesting greater activation of the Th17 arm during the immune response when compared to Wt mice. The survival of Th17 deficient IL-23p19-/- mice was similar to Wt mice.;Taken together, these findings demonstrate that CD4+ T cells are not required for the recruitment of neutrophils to the lungs after pulmonary challenge with ST3 and suggest that CD8+ T cells could function as immunomodulators that dampen the inflammatory response to this ST in mice.