Lymphocyte apoptosis in murine Pneumocystis pneumonia.
BACKGROUND
Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs.


METHODS
Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins.


RESULTS
In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim.


CONCLUSIONS
Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins.
Shi
Xin
X
Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, New Orleans, LA 70112, USA. xshi@lsuhsc.edu
LeCapitaine
Nicole J
NJ
Rudner
Xiaowen L
XL
Ruan
Sanbao
S
Shellito
Judd E
JE
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D018941:Antigens, CD19; D017209:Apoptosis / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008214:Lymphocytes / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011020:Pneumonia, Pneumocystis / Q000382:microbiology / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology
D017304:Annexin A5; D018941:Antigens, CD19; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D020169:Caspases