Induction of CD1-Restricted Immune Responses in Guinea Pigs by Immunization with Mycobacterial Lipid Antigens

• Published in: The Journal of immunology (1950) Vol. 169; no. 1; pp. 330 - 339
• Main Authors: Hiromatsu, Kenji, Dascher, Christopher C, LeClair, Kenneth P, Sugita, Masahiko, Furlong, Stephen T, Brenner, Michael B, Porcelli, Steven A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.07.2002
• Subjects: Animals; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - immunology; Antigens, CD1 - immunology; Bone Marrow Cells - immunology; Bone Marrow Transplantation; Cell Culture Techniques - methods; Cell Line; Cells, Cultured; Cytotoxicity Tests, Immunologic; Dendritic Cells - immunology; Dendritic Cells - transplantation; Epitopes, T-Lymphocyte - immunology; Female; Guinea Pigs; Immunization; Immunophenotyping; Injections, Subcutaneous; Lipids - administration & dosage; Lipids - immunology; Lymphocyte Activation - immunology; Mycobacterium tuberculosis - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.1.330

Group 1 CD1 molecules have been shown to present lipid and glycolipid Ags of mycobacteria to human T cells. However, a suitable animal model for the investigation of this component of antimycobacterial immunity has not yet been established. Previously, we found that guinea pigs express multiple isoforms of group 1 CD1 proteins that are homologous to human CD1b and CD1c. In this study, we show that CD1-restricted T cell responses can be generated in guinea pigs following immunization with lipid Ags from Mycobacterium tuberculosis. Splenic T cells from lipid Ag-immunized guinea pigs showed strong proliferative responses to total lipid Ags and partially purified glycolipid fractions from M. tuberculosis. These lipid Ag-reactive T cells were enriched in CD4-negative T cell fractions and showed cytotoxic activity against CD1-expressing guinea pig bone marrow-derived dendritic cells pulsed with M. tuberculosis lipid Ags. Using guinea pig cell lines transfected with individual CD1 isoforms as target cells in cytotoxic T cell assays, we found that guinea pig CD1b and CD1c molecules presented M. tuberculosis glycolipid Ags to T cells raised by mycobacterial lipid immunization. These results were confirmed using a T cell line derived from M. tuberculosis lipid Ag-immunized guinea pigs, which also showed CD1-restricted responses and cytolytic activity. Our results demonstrate that CD1-restricted responses against microbial glycolipid Ags can be generated in vivo by specific immunization and provide support for the use of the guinea pig as a relevant small animal model for the study of CD1-restricted immune responses to mycobacterial pathogens.