Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens

Kenji Hiromatsu, Christopher C. Dascher, Kenneth P. LeClair, Masahiko Sugita, Stephen T. Furlong, Michael B. Brenner, Steven A. Porcelli

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)330-339
Number of pages10
JournalJournal of Immunology
Volume169
Issue number1
StatePublished - Jul 1 2002

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Immunization
Guinea Pigs
T-Lymphocytes
Lipids
Antigens
Mycobacterium tuberculosis
Glycolipids
Protein Isoforms
Animal Models
Cell Line
Mycobacterium
Dendritic Cells
Immunity
Bone Marrow
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Hiromatsu, K., Dascher, C. C., LeClair, K. P., Sugita, M., Furlong, S. T., Brenner, M. B., & Porcelli, S. A. (2002). Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. Journal of Immunology, 169(1), 330-339.

Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. / Hiromatsu, Kenji; Dascher, Christopher C.; LeClair, Kenneth P.; Sugita, Masahiko; Furlong, Stephen T.; Brenner, Michael B.; Porcelli, Steven A.

In: Journal of Immunology, Vol. 169, No. 1, 01.07.2002, p. 330-339.

Research output: Contribution to journalArticle

Hiromatsu, K, Dascher, CC, LeClair, KP, Sugita, M, Furlong, ST, Brenner, MB & Porcelli, SA 2002, 'Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens', Journal of Immunology, vol. 169, no. 1, pp. 330-339.
Hiromatsu K, Dascher CC, LeClair KP, Sugita M, Furlong ST, Brenner MB et al. Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. Journal of Immunology. 2002 Jul 1;169(1):330-339.
Hiromatsu, Kenji ; Dascher, Christopher C. ; LeClair, Kenneth P. ; Sugita, Masahiko ; Furlong, Stephen T. ; Brenner, Michael B. ; Porcelli, Steven A. / Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens. In: Journal of Immunology. 2002 ; Vol. 169, No. 1. pp. 330-339.
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