Lung CD25 CD4 regulatory T cells suppress type 2 immune responses but not bronchial hyperreactivity.
To study the effects of chronic Ag deposition in the airway mucosa on CD4(+) T cell priming and subsequent airway disease, transgenic mice were generated that expressed OVA under the control of the surfactant protein C promoter. CD4 T cells from these mice were tolerant to OVA but this was overcome among spleen CD4 T cells by crossing to OVA-specific DO11.10 TCR-transgenic mice. Lungs from the double-transgenic mice developed lymphocytic infiltrates and modest mucus cell hyperplasia. Infiltrating cells were unaffected by the absence of either Rag-1 or Stat6, although the latter deficiency led to the disappearance of mucus. In the lung of double-transgenic mice, a large number of Ag-specific CD4 T cells expressed CD25 and functioned as regulatory T cells. The CD25(+) CD4 T cells suppressed proliferation of CD25(-) CD4 T cells in vitro and inhibited type 2 immune responses induced by aerosolized Ags in vivo. Despite their ability to suppress allergic type 2 immunity in the airways, however, CD25(+) CD4 regulatory T cells had no effect on the development of bronchial hyperreactivity.
Hadeiba
Husein
H
Department of Medicine, University of California, San Francisco, CA 94143, USA.
Locksley
Richard M
RM
D000281:Administration, Intranasal; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D003433:Crosses, Genetic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007108:Immune Tolerance / Q000235:genetics; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016131:Lymphocyte Subsets / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D050800:STAT6 Transcription Factor; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D019076:Transgenes / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D018398:Homeodomain Proteins; D037721:Pulmonary Surfactant-Associated Protein C; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; C064658:RAG-1 protein; D010047:Ovalbumin