Differences in the Reactivity of CD4+ T‐Cell Lines Generated against Free Versus Nucleosome‐Bound SV40 Large T Antigen

• Published in: Scandinavian journal of immunology Vol. 53; no. 4; pp. 372 - 380
• Main Authors: Bredholt, G., Rekvig, O.P., Andreassen, K., Moens, U., Marion, T.N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.04.2001; Wiley Subscription Services, Inc
• Subjects: Animals; Antigen Presentation; Antigens, Polyomavirus Transforming - immunology; Autoimmunity; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell Division; Cell Line; Humans; Immunization; In Vitro Techniques; Lymphocyte Activation; Mice; Nucleosomes - immunology; Solubility
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.2001.00873.x

Previous results have revealed a strong correlation between polyomavirus BK reactivation and disease activity and antinuclear auto‐antibody production in the human autoimmune disease systemic lupus erythematosus. BK virus establishes a latent infection in most humans, and reactivation requires the production of the DNA‐binding large T antigen. Experimentally induced expression of the polyomavirus SV40 large T antigen in mice induces both an immune response to large T antigen and autoimmune response to nuclear antigens and antinuclear antibody production. Previous results have indicated that human T‐antigen‐specific CD4+ T‐cell lines are stimulated equally by free, soluble and nucleosome‐bound T antigen. This study was designed to determine how antigen processing of nucleosomes containing bound SV40 large T antigen may affect the specificity and response characteristics of experimentally induced T‐antigen‐specific CD4+ T cells. The results indicated that CD4+ T‐cell lines generated from mice immunized with soluble, free T antigen responded very poorly in response to stimulation with T antigen bound to nucleosomes. CD4+ T‐cell lines generated from mice immunized with nucleosomes that had bound T antigen in situ responded to both free and nucleosome‐bound T antigen. The T‐antigen‐specific, CD4+ memory T cells induced by latent polyomavirus infections in humans may be uniquely suited to initiate autoimmunity to nuclear antigens upon virus reactivation.