Lung antigen induced cell-mediated immune injury in chronic respiratory diseases.

Abstract

A soluble connective tissue extract was obtained by treatment of washed guinea pig, rat, and human lung connective tissue with pH 3.2 citrate buffer. Partial characterization of the preparation indi­ cated at least 2 potential antigenic fractions: a weakly reactive mucopolysaccharide moiety and a more strongly reactive fibrous protein fraction probably derived from elastin or collagen. Normal guinea pigs were sensitized by subcutaneous and intramuscular injections of the extract admixed in Freund's complete adjuvant. In vivo and in vitro assessments of delayed hypersensitivity to the connective tissue extract were conducted 3 to 4 weeks after sensitization with the following results: (1) skin test reactions consisting of induration and erythema in 14 of 2J animals; (2) confirmation of skin test reactions by histopathologic criteria in 8 of 10 random biopsies of challenged, sensitized animals; (3) specific migration inhibition of sensitized peritoneal exudate cells ranging from 23 to 68 per cent in 10 of II animals; (4) cytotoxic destruction of target cell monolayers due to release of lymphotoxin generated by sensitized lymphoid cells incubated in the presence of the connective tissue extract in 4 of 5 test situations. Successful passive transfer of the delayed hypersensitive state was accomplished with living sensitized donor cells. A consistent increase in pathologic changes in the lungs at 8- and 16-week intervals was observed in animals sensitized with the connective tissue extract in Freund's complete adjuvant as compared with animals immunized with Freund's complete adjuvant alone. Delayed autoallergy to the extract was demonstrated in 3 experimental diseases (tuberculosis, berylliosis, and pneumoconiosis) in the guinea pig and rat, and suggestive evidence of similar participation of delayed autoallergy to antigen(s) in the connective tissue extract was obtained in 3 of 9 human subjects with chronic pulmonary disorders.