CD8 T Cells Modulate CD4 T-Cell and Eosinophil-Mediated Pulmonary Pathology in Pneumocystis Pneumonia in B-Cell-Deficient Mice

Swain, Steve D.; Meissner, Nicole; Harmsen, Allen G.

doi:10.2353/ajpath.2006.050724

Cited by 37 publications

(36 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data show a much lower cumulative incidence and prevalence of asthma in HIV+ HAART− children than HIV + HAART+ children and a restoration of the risk of asthma when HIV+ children were treated with HAART. This pediatric human model of asthma confirms what has been seen in animal models with asthma [1][2][3] and suggests that the loss of CD4 + T cells in children with untreated HIV infection protects against asthma, and the gain of CD4 + T cells with HAART therapy serves as a risk factor for asthma. Our findings are in agreement with most studies of adult patients with HIV infection [5][6][7][8] but not other studies.…”

Section: Discussionsupporting

confidence: 80%

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Foster

McIntosh

Thompson

et al. 2008

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 80%

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Foster

McIntosh

Thompson

et al. 2008

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…At 30 days postinfection, there was an elevation of total CD3 ϩ T cells and Ly6G ϩ F4/80 Ϫ neutrophils within the lungs of B cell Ϫ/Ϫ mice. Notably, there is a significant increase of CD8 ϩ T cells in B cell Ϫ/Ϫ lungs, which may be the result of the host response to the exacerbated inflammation observed in the infected B cell Ϫ/Ϫ mice, as CD8 ϩ T cells have been reported to protect against inflammatory pathology in murine models of Pneumocystis and Mycoplasma infection (43,44). An alternative explanation is that in the absence of B cells, there is an increased expansion or migration of neutrophils and CD8…”

Section: Discussionmentioning

confidence: 99%

B Cells Moderate Inflammatory Progression and Enhance Bacterial Containment upon Pulmonary Challenge withMycobacterium tuberculosis

Maglione

Chan

2007

The Journal of Immunology

268

320

View full text Add to dashboard Cite

Though much is known about the function of T lymphocytes in the adaptive immune response against Mycobacterium tuberculosis, comparably little is understood regarding the corresponding role of B lymphocytes. Indicating B cells as components of lymphoid neogenesis during pulmonary tuberculosis, we have identified ectopic germinal centers (GCs) in the lungs of infected mice. B cells in these pulmonary lymphoid aggregates express peanut agglutinin and GL7, two markers of GC B cells, as well as CXCR5, and migrate in response to the lymphoid-associated chemokine CXCL13 ex vivo. CXCL13 is negatively regulated by the presence of B cells, as its production is elevated in lungs of B cell-deficient (B cell−/−) mice. Upon aerosol with 100 CFU of M. tuberculosis Erdman, B cell−/− mice have exacerbated immunopathology corresponding with elevated pulmonary recruitment of neutrophils. Infected B cell−/− mice show increased production of IL-10 in the lungs, whereas IFN-γ, TNF-α, and IL-10R remain unchanged from wild type. B cell−/− mice have enhanced susceptibility to infection when aerogenically challenged with 300 CFU of M. tuberculosis corresponding with elevated bacterial burden in the lungs but not in the spleen or liver. Adoptive transfer of B cells complements the phenotypes of B cell−/− mice, confirming a role for B cells in both modulation of the host response and optimal containment of the tubercle bacillus. As components of ectopic GCs, moderators of inflammatory progression, and enhancers of local immunity against bacterial challenge, B cells may have a greater role in the host defense against M. tuberculosis than previously thought.

show abstract

“…There are little data regarding the role these cells play during Pneumocystis infection. It was recently shown that the ratio of CD4 ϩ CD25 ϩ /CD4 ϩ CD25 Ϫ T cells in the bronchoalveolar lavage (BAL) fluid is altered in B cell-deficient mice (MT) depleted of CD8 ϩ T cells following Pneumocystis infection (11). Moreover, these CD8-depleted MT mice exhibit an exacerbated Th2 phenotype and increased lung injury (11).…”

mentioning

confidence: 99%

Regulatory T Cells Dampen Pulmonary Inflammation and Lung Injury in an Animal Model ofPneumocystisPneumonia

McKinley

Logar

McAllister

et al. 2006

The Journal of Immunology

103

View full text Add to dashboard Cite

CD4+CD25+FoxP3+ regulatory T cells are decreased in patients infected with HIV and have been shown to be critical in mediating Ag tolerance in the lung. Because a subset of Pneumocystis-infected individuals develop substantial lung injury, which can be modeled in immune reconstituted scid mice, we used mouse models of Pneumocystis carinii to investigate the role of regulatory T cells in opportunistic infection and immune reconstitution. In this study, we show that CD4+CD25+FoxP3+ cells are part of the host response to Pneumocystis in CD4+ T cell-intact mice. Moreover, lung injury and proinflammatory Th1 and Th2 cytokine levels in the bronchoalveolar lavage fluid and lung homogenate were increased following CD4+CD25− immune reconstitution in Pneumocystis-infected SCID mice but not in CD4+CD25+ T cell-reconstituted animals. The ability of CD4+CD25+ T cells to control inflammation and injury during the course of Pneumocystis was confirmed by treatment of wild-type C57BL/6 mice with anti-CD25 mAb. These data show that CD4+CD25+ T cells control pulmonary inflammation and lung injury associated with Pneumocystis infection both in the setting of immune reconstitution as well as new acquisition of infection.

show abstract

CD8 T Cells Modulate CD4 T-Cell and Eosinophil-Mediated Pulmonary Pathology in Pneumocystis Pneumonia in B-Cell-Deficient Mice

Cited by 37 publications

References 54 publications

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study

B Cells Moderate Inflammatory Progression and Enhance Bacterial Containment upon Pulmonary Challenge withMycobacterium tuberculosis

Regulatory T Cells Dampen Pulmonary Inflammation and Lung Injury in an Animal Model ofPneumocystisPneumonia

Contact Info

Product

Resources

About