The pulmonary environment promotes Th2 cell responses after nasal-pulmonary immunization with antigen alone, but Th1 responses are induced during instances of intense immune stimulation

The purpose of this study was to determine the nature of the CD4(+) Th cell responses induced after nasal-pulmonary immunization, especially those coi nciding with previously described pulmonary, inflammation associated with t he use of the mucosal adjuvant, cholera toxin (CT). The major T cell popula tion in the lungs of naive mice was CD4+, and these cells were shown to be predominantly of Th2 type as in vitro polyclonal stimulation resulted in IL -4, but not IFN-gamma, production. After nasal immunization with influenza Ag alone, Th2 cytokine mRNA (IL-4 and IL-5) levels were increased, whereas there was no change in Th1 cytokine (IL-2 and IFN-gamma) mRNA expression. T he use of the mucosal adjuvant, CT, markedly enhanced pulmonary Th2-type re sponses; however, there was also a Th1 component to the T cell response. Us ing in vitro Ag stimulation of pulmonary lymphocytes, influenza virus-speci fic cytokine production correlated with the mRNA cytokine results. Furtherm ore, there was a large increase in CD4(+) Th cell numbers in lungs after na sal immunization using CT, correlating with the pulmonary inflammatory infi ltrate previously described. Coincidentally, both macrophage-inflammatory p rotein-1 alpha (MIP-1 alpha) and MIP-1 beta mRNA expression increased in th e lungs after immunization with Ag plus CT, while only MIP-1 beta expressio n increased when mice were given influenza Ag alone. Our study suggests a m echanism to foster Th1 cell recruitment into the lung, which may impact on pulmonary immune responses. Thus, while Th2 cell responses may be prevalent in modulating mucosal immunity in the lungs, Th1 cell responses contribute to pulmonary defenses during instances of intense immune stimulation.