Contribution of T cell subsets to the pathophysiology ofPneumocystis-related immunorestitution disease
| Autor: | Terry W. Wright, Francis Gigliotti, Samir P. Bhagwat, Haodong Xu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pulmonary and Respiratory Medicine
Physiology T cell Mice SCID CD8-Positive T-Lymphocytes Lung injury Biology Pneumocystis carinii Pneumocystis pneumonia Polymerase Chain Reaction Article Mice Interleukin 21 T-Lymphocyte Subsets Physiology (medical) parasitic diseases medicine Animals Serine Endopeptidases Cell Biology medicine.disease Pathophysiology CD4 Lymphocyte Count Pneumocystis Infections medicine.anatomical_structure Immunology Female CD8 |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 291:L1256-L1266 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00079.2006 |
| Popis: | Immune-mediated lung injury is an important component of Pneumocystis pneumonia (PcP)-related immunorestitution disease (IRD). However, the individual contribution of CD4+and CD8+T cells to the pathophysiology of IRD remains undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice, and specific T cell depletion was used to determine how T cell subsets interact to affect the nature and severity of disease. CD4+cells were more abundant than CD8+cells during the acute stage of IRD that coincided with impaired pulmonary physiology and organism clearance. Conversely, CD8+cells were more abundant during the resolution phase following P. carinii clearance. Depletion of CD4+T cells protected mice from the acute pathophysiology of IRD. However, these mice could not clear the infection and developed severe PcP at later time points when a pathological CD8+T cell response was observed. In contrast, mice depleted of CD8+T cells efficiently cleared the infection but developed more severe disease, an increased frequency of IFN-γ-producing CD4+cells, and a prolonged CD4+T cell response than mice with both CD4+and CD8+cells. These data suggest that CD4+T cells mediate the acute respiratory disease associated with IRD. In contrast, CD8+T cells contributed to neither lung injury nor organism clearance when CD4+cells were present, but instead served to modulate CD4 function. In the absence of CD4+cells, CD8+T cells produced a nonprotective, pathological immune response. These data suggest that the interplay of CD4+and CD8+T cells affects the ultimate outcome of PcP-related IRD. |
| Databáze: | OpenAIRE |
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