Experimental murine hypersensitivity pneumonitis: multigenic control and influence by genes within the I-B subregion...

An animal model of hypersensitivity pneumonitis was developed in the mouse by immunization with pigeon dropping extract (PDE) in complete Freund's adjuvant, followed by daily aerosol challenge with soluble specific antigen. C3H/He (H-2k) mice developed intense diffuse interstitial lung disease and were classified as high responders. On the other hand C57BL/10 (H-2b) mice developed only mild perivascular infiltration. Moreover, although high-responder C3H/He mice developed delayed hypersensitivity to PDE, low-responder C57BL/10 mice failed to develop this reactivity. Breeding studies in F1 and F2 progeny of C3H/He high responders and C57BL/10 low responders showed that responsiveness was multigenic. B10.BR (H-2k) mice also developed intense PDE-induced diffuse interstitial lung disease, suggesting that genes within the H-2 complex influence the development of pulmonary inflammation. On the other hand, C3H.SW (H-2b) mice were also high responders, possibly because of non-H-2 genes in the C3H/He background that influenced responsiveness. Studies in H-2 recombinant strains with C57BL/10 backgrounds mapped the H-2-linked genes that influence responsiveness within the I-B subregion.