Immunity to Rhodococcus equi: antigen-specific recall responses in the lungs of adult horses

Rhodococcal pneumonia is an important disease of young horses that is not s een in immunocompetent adults. Since all foals are normally exposed to Rhod ococcus equi in their environment, we hypothesized that most develop protec tive immune responses. Furthermore, these antigen-specific responses were h ypothesized to operate throughout adult life to prevent rhodococcal pneumon ia. A better understanding of the mechanisms of immune clearance in adult h orses would help define the requirements for an effective vaccine in foals. Adult horses were challenged with virulent R. equi by intrabronchial inocu lation into the right lung, and pulmonary immune responses were followed fo r 2 weeks by bronchoalveolar lavage. Local responses in the inoculated righ t lung were compared to the uninfected left lung and peripheral blood. Chal lenged horses rapidly cleared R. equi infection without significant clinica l signs. Clearance of bacteria was associated with increased mononuclear ce lls in bronchoalveolar lavage fluid (primarily lymphocytes) and inversion o f the normal macrophage:lymphocyte ratio. There was no significant increase in neutrophils at 7 days post-challenge. Flow cytometric analysis of bronc hoalveolar lavage fluid demonstrated that clearance correlated with signifi cant increases in pulmonary T-lymphocytes, both CD4+ and CD8+. Prior to cha llenge, most adult horses demonstrated low proliferative responses when pul monary lymphocytes were stimulated with soluble R. equi ex vivo. However, c learance was associated with marked increases in lymphoproliferative respon ses to soluble R. equi antigen and recombinant VapA, a virulence associated protein of R. equi and candidate immunogen. These results are compatible w ith previous work in mice which showed that both CD4+ and CD8+ T-cells play a role in immune clearance of R. equi. Recognition of VapA in association with clearance lends further support to its testing as an immunogen. Import antly, the cellular responses to R. equi challenge were relatively compartm entalized. Responses were more dmarked and the sensitivity to antigen dose was increased at the site of challenge. The blood, including peripheral blo od mononuclear cells, was an insensitive indicator of local pulmonary respo nses. (C) 2001 Elsevier Science B.V. All rights reserved.