Importance of Serotype-related Antigen in the Induction of Experimental Hypersensitivity Pneumonitis byTrichosporon cutaneumin Rabbits: Correlation between Granulomatous Alveolitis and Cellular and Humoral Immune Responses to Polysaccharide-rich Antigen

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Abstract
We evaluated the immunopathogenic properties of Trichosporon cutaneum, a major etiologic agent of Japanese summer-type hypersensitivity pneumonitis (HP). When the culture filtrate antigen of T. cutaneum was chromatographed on DEAE-cellulose, two peaks of polysaccharide, fractions A and B, were obtained. Fraction B was highly reactive to the specific IgG and IgA antibodies in the serum and bronchoalveolar lavage fluid samples obtained from sensitized rabbits, whereas fraction A was mainly reactive to the IgG antibodies. When the rabbits sensitized by intratracheal injection with the particulate antigen of T. cutaneum were challenged intratracheally by these antigenic fractions, fraction B induced granulomatous alveolitis, but fraction A induced granulomatous alveolitis, but fraction A induced alveolitis rather than granuloma. Lymphocytes of the mediastinal lymph nodes responded prominently to fraction B, but less to fraction A, as assessed by proliferative response. Each of the fractions B obtained from two strains of different serotypes (TIMM 1573, serotype I and TIMM 1318, serotype II) was reactive in enzyme-linked immunosorbent assay to the serum samples from the rabbits sensitized with homologous antigen, but far less to that from the rabbits sensitized with heterologous antigen, that is, the antigenic specificity of fraction B was related to the serotype of T. cutaneum. Fractionation by gel filtration on Sepharose CL-4B revealed that the molecular weight of the antigenic components in fraction B was larger than 1,000,000 and that the components consisted mainly of polysaccharide. In immunodiffusion, the high molecular weight fractions of serotypes I and II showed precipitin lines reacting with each of the homologous antisera, but no line with the heterologous antisera. This antigenic activity was sodium-periodate-sensitive and pronase-insensitive, suggesting a polysaccharide nature. We conclude that the serotype-related polysaccharide antigen(s) of T. cutaneum induces both cellular and humoral immune responses, resulting in the production of granulomatous alveolitis in experimental HP.