title: Antigen-nonspecific recruitment of Th2 cells to the lung as a mechanism for viral infection-induced allergic asthma.
abstract: Respiratory viral infections have been shown to trigger exacerbations of asthma; however, the mechanism by which viral Th1-type inflammation exacerbates an allergic Th2-type disease remains unclear. We have previously shown that although adoptively transferred Th2 cells are inefficiently recruited to the lung in response to Ag, cotransfer of Th1 cells can increase accumulation of Th2 cells. In this study, we show that respiratory viral infection increases recruitment of resting Th2 cells specific for OVA even in the absence of OVA challenge. These findings suggest that the mechanism by which Th1-type inflammation enhances allergy is via an effect on recruitment. To study the role of the antigenic specificity of Th1 cells in the enhancement of Th2 cell recruitment and to determine whether virus-induced recruitment of OVA-specific Th2 cells may involve Th1 cells specific to a different Ag, we tested whether hen egg lysozyme-specific Th1 cells could synergize with OVA-specific Th2 cells. Challenge of mice that had received adoptively transferred Th1 cells plus Th2 cells induced the expression of inflammatory chemokines in the lung and increased both recruitment and activation of Th2 cells, leading to eosinophil recruitment, even in the absence of challenge with the Th2 Ag. Interestingly, as IL-5 supports eosinophilia, culture of resting Th2 cells with fresh APC induced production of IL-5 in the absence of specific Ag. Thus, Ag-specific activation of Th1 cells enhances the recruitment potential of the lung leading to recruitment and activation of Th2 cells. This implies that circulating Th2 cells in allergic individuals could enter the lungs in response to infection or inflammation and become activated to trigger allergy.
authors.affiliation: Center for Immunology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Stephens
authors.forename: David A
authors.initials: DA
authors.lastname: Randolph
authors.forename: Guangming
authors.initials: G
authors.lastname: Huang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
mesh_terms: D000818:Animals; D000955:Antigens, T-Independent / Q000502:physiology; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D005260:Female; D016130:Immunophenotyping; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D010253:Respirovirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D029082:Sendai virus / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014132:Trachea; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000955:Antigens, T-Independent; D018925:Chemokines; D018984:Epitopes, T-Lymphocyte; D015848:Interleukin-5