Th2-induced eotaxin expression and eosinophilia coexist with Th1 responses at the effector stage of lung inflammation.
The T cell-mediated lung inflammation that is associated with allergic asthma is characterized mainly by massive eosinophil infiltration, which induces airway injury and the subsequent late-phase reactivity. Because Th2 cells are often isolated from asthmatic subjects, these cells are postulated to play a role in asthma pathogenesis. We report that adoptively transferred, influenza hemagglutinin-specific Th1 and Th2 cells induced different patterns of chemokines leading to different types of cellular infiltration. Th2 cells were sufficient to induce dramatic Ag-dependent lung eosinophilia and eotaxin expression; by contrast, Th1 transfer primarily induced neutrophil recruitment with little eotaxin production. To determine whether Th1 cells show inhibitory effects on Th2 cell-mediated responses, Th1 and Th2 cells were cotransferred. Hemagglutinin-specific Th1 cells did not inhibit Ag-induced lung eosinophilia, nor did they inhibit eotaxin expression. Furthermore, influenza virus infection of the lung in mice receiving hemagglutinin-specific Th2 cells also induced eotaxin expression and eosinophilia that could not be inhibited by the cotransfer of Th1 cells. Our results show that Th2-mediated allergic lung inflammation coexists with the Th1-mediated responses that are stimulated by diverse forms of Ags.
Li
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L
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Xia
Y
Y
Nguyen
A
A
Feng
L
L
Lo
D
D
D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte