Immunological tolerance to hapten prevents subsequent induction of hapten-immune pulmonary interstitial fibrosis (HIPIF).
Pulmonary interstitial fibrosis (PIF) is a morphological term which in part can be defined as accumulation of collagen in the extracellular matrix. Previously we showed that hamsters sensitized with 2,4,6-trinitro-1-chlorobenzene (TNCB) developed PIF 14 days after an intratracheal challenge with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The participation of delayed-type hypersensitivity (DTH) in lung collagen deposition was clearly demonstrated. In this paper, we use an adaptation of this model to mice and show that the lung collagen deposition observed was related to the genetic ability of the strain to maintain a DTH response to the immunizing hapten (TNP). Specifically, the lung collagen deposition on Day 14 in hapten-sensitized, challenged animals in high responder to TNP (BALB/c, H-2d) was higher than that in low responder mouse (C57BL/6, H-2b). Furthermore, aged C57BL/6 strain (retired breeders) possessed a DTH response to TNP and produced significantly higher accumulation of hydroxyproline than that of TNBS-challenged-only animals. A DTH mechanism for the induction of the fibrosis is consistent with the observation that responder mice that were made tolerant to the antigen were unable to respond to the lung challenge with a specific increase in lung index or collagen deposition. These results suggest that effector T lymphocytes that are important in DTH play a key role in the regulation of lung collagen deposition in hapten-immune pulmonary interstitial fibrosis (HIPIF) in mice.
Kimura
R
R
Department of Medicine, University of Miami School of Medicine, Florida 33101.
Hu
H
H
Stein-Streilein
J
J
D000367:Age Factors; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology; D005260:Female; D006241:Haptens / Q000276:immunology*; D006909:Hydroxyproline / Q000032:analysis; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000517:prevention & control*
D006241:Haptens; D003094:Collagen; D006909:Hydroxyproline