Contribution of T cell subsets to the pathophysiology of Pneumocystis-related immunorestitution disease.
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-gamma-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.
Bhagwat
Samir P
SP
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Gigliotti
Francis
F
Xu
Haodong
H
Wright
Terry W
TW
D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051379:Mice; D016513:Mice, SCID; D016720:Pneumocystis Infections / Q000276:immunology* / Q000473:pathology; D045363:Pneumocystis carinii; D016133:Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
C470926:Kex1 protein, Pneumocystis jirovecii; D012697:Serine Endopeptidases