Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens.
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.
Hiromatsu
Kenji
K
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Dascher
Christopher C
CC
LeClair
Kenneth P
KP
Sugita
Masahiko
M
Furlong
Stephen T
ST
Brenner
Michael B
MB
Porcelli
Steven A
SA
D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D008055:Lipids / Q000008:administration & dosage* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D018984:Epitopes, T-Lymphocyte; D008055:Lipids