T helper cell responses in lungs after immunization and chronic respiratory disease and their association with pulmonary inflammation

The purpose of these studies was to characterize T helper cell responses in the lungs of mice after immunization and chronic respiratory infection. Polyclonal activation of resident CD4+ T cells produced abundant levels of IL-4 in comparison to IFN-gamma, indicating that Th2 cells were the major sub-population of CD4+ T cells. In contrast, resident CD8+ T cells were the sole producer of IFN-gamma by naive T lymphocytes. Furthermore, the distribution of T cells was similar between BALB/c, C3H/HeN, C57BL/6 and DBA/2N strains of mice. However differences in the distribution of CD8+ T cells, as well as the levels of IL-4 and IFN-gamma production produced by resident T cells were found between C57 and the other strains of mice tested. These results demonstrate that host genetic factors may be involved in determining host susceptibility to respiratory disease.;Differences in the intensity of antigenic stimulation provoke changes in the type of T cell response generated.;Chronic respiratory infection also elicited changes in the resident population of T cells consistent with pulmonary inflammatory immune responses. At early stages of infection, CD4+, but not CD8+ T cells increased in number within inductive respiratory lymphoid tissues (lower respiratory nodes [LRNs]). Mycoplasma-specific IL-4 and IFN-gamma production also increased in a tissue-specific/time-dependent manner. IL-4 production was initially observed in the LRNs, whereas significant levels of IL-4 and IFN-gamma was produced in both tissues 14 days after infection. In comparison, IFN-gamma was the predominate cytokine, produce at 14 days coinciding with pulmonary inflammation.;Both CD4+ and CD8+ T cells were shown to have a role in modulation of disease severity during mycoplasma disease.;We find that mycoplasama increase the number of dendritic cells in the lung 14 days after infection, and stimulated the production of dendritic cell-derived ABCD-1 chemokine. Also, beta-chemokine MIP-1alpha and MIP-1beta production was observed during intense immunization as well as during mycoplasma infection. These results provide evidence for a potential mechanism through which changes in resident pulmonary T cell responses occur given the intensity of the immune response generated. (Abstract shortened by UMI.)...