title: CD4(+) T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia.
abstract: Pneumocystis pneumonia is a major cause of morbidity and mortality among immunocompromised patients, especially in the context of HIV/AIDS. In the murine model of Pneumocystis pneumonia, CD4(+) T-cells are required for clearance of a primary infection of Pneumocystis, but not the memory recall response. We hypothesized that the memory recall response in the absence of CD4(+) T-cells is mediated by a robust memory humoral response, CD8(+) T-cells, and IgG-mediated phagocytosis by alveolar macrophages. To investigate the role of CD8(+) T-cells and alveolar macrophages in the immune memory response to Pneumocystis, mice previously challenged with Pneumocystis were depleted of CD8(+) T-cells or alveolar macrophages prior to re-infection. Mice depleted of CD4(+) T-cells prior to secondary challenge cleared Pneumocystis infection within 48 h identical to immunocompetent mice during a secondary memory recall response. However, loss of CD8(+) T-cells or macrophages prior to the memory recall response significantly impaired Pneumocystis clearance. Specifically, mice depleted of CD8(+) T-cells or alveolar macrophages had significantly higher fungal burden in the lungs. Furthermore, loss of alveolar macrophages significantly skewed the lung CD8(+) T-cell response toward a terminally differentiated effector memory population and increased the percentage of IFN-γ(+) CD8(+) T-cells. Finally, Pneumocystis-infected animals produced significantly more bone marrow plasma cells and Pneumocystis-specific IgG significantly increased macrophage-mediated killing of Pneumocystis in vitro. These data suggest that secondary immune memory responses to Pneumocystis are mediated, in part, by CD8(+) T-cells, alveolar macrophages, and the production of Pneumocystis-specific IgG.
authors.affiliation: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: de la Rua
authors.affiliation: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors.forename: Derrick R
authors.initials: DR
authors.lastname: Samuelson
authors.affiliation: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors.forename: Tysheena P
authors.initials: TP
authors.lastname: Charles
authors.affiliation: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Welsh
authors.affiliation: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA , USA.
authors.forename: Judd E
authors.initials: JE
authors.lastname: Shellito
keywords: BMPCs; CD8+ T-cells; Pneumocystis; immune memory; macrophages; pneumonia