Effect of a CD4-depleting antibody on the development of Cryptococcus neoformans-induced allergic bronchopulmonary mycosis in mice.
Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity lung disease in which fungal colonization is accompanied by an allergic response to the fungus. Using a mouse model of ABPM caused by Cryptococcus neoformans infection of C57BL/6 mice, the goal of the present studies was to determine the effect of the CD4-depleting monoclonal antibody GK1.5 on the development of the allergic responses seen during active fungal infection. These results would provide insight into the role of CD4(+) T cells in this disease. Our results show that GK1.5 treatment resulted in attenuation of pulmonary inflammation and eosinophilia in these animals. These mice also had reduced T2 cytokine production and no serum immunoglobulin E production. Absence of CD4(+) T cells did not affect recruitment of CD8(+) T cells to the site of infection; however, the numbers of CD19(+) B cells were severely reduced in the lungs of CD4(+) T-cell-depleted animals. We also examined changes in the pulmonary architecture and found that depletion of CD4(+) T cells was associated with a significant reduction in mucus production and goblet cell metaplasia in these mice. Interestingly, attenuation of Th2 responses in CD4(+) T-cell-depleted animals did not increase the fungal load in their lungs. We also compared development of ABPM in young and mature mice and did not find any differences at any of the time points. Overall, our results show that depletion of CD4(+) T cells prevents the development of Th2 responses seen during ABPM.
Arora
Shikha
S
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA.
McDonald
Roderick A
RA
Toews
Galen B
GB
Huffnagle
Gary B
GB
D000367:Age Factors; D000818:Animals; D000908:Antibodies, Fungal / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003453:Cryptococcosis / Q000276:immunology* / Q000473:pathology; D003455:Cryptococcus neoformans / Q000276:immunology*; D005260:Female; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology
D000908:Antibodies, Fungal