Rapid Clonal Expansion and Prolonged Maintenance of Memory Cd8+ T Cells of the Effector (Cd44highcd62llow) and Central (Cd44highcd62lhigh) Phenotype by an Archaeosome Adjuvant Independent of Tlr2.
From: National Research Council-Institute for Biological Sciences, Ottawa, Ontario, Canada. Lakshmi.Krishnan@nrc-cnrc.gc.ca
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Feb 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 4
- Pages: 2396-406
- Medium: Print
- Language: English
- Citation (JAMA): Krishnan Lakshmi, Gurnani Komal, Dicaire Chantal J, et al. Rapid Clonal Expansion and Prolonged Maintenance of Memory Cd8+ T Cells of the Effector (Cd44highcd62llow) and Central (Cd44highcd62lhigh) Phenotype by an Archaeosome Adjuvant Independent of Tlr2.. J. Immunol. Feb 2007;178:2396-406
Abstract
Vaccines capable of eliciting long-term T cell immunity are required for combating many diseases. Live vectors can be unsafe whereas subunit vaccines often lack potency. We previously reported induction of CD8(+) T cells to Ag entrapped in archaeal glycerolipid vesicles (archaeosomes). In this study, we evaluated the priming, phenotype, and functionality of the CD8(+) T cells induced after immunization of mice with OVA-Methanobrevibacter smithii archaeosomes (MS-OVA). A single injection of MS-OVA evoked a profound primary response but the numbers of H-2K(b)OVA(257-264)-specific CD8(+) T cells declined by 14-21 days, and <1% of primarily central phenotype (CD44(high)CD62L(high)) cells persisted. A booster injection of MS-OVA at 3-11 wk promoted massive clonal expansion and a peak effector response of approximately 20% splenic/blood OVA(257-264)-specific CD8(+) T cells. Furthermore, contraction was protracted and the memory pool (IL-7Ralpha(high)) of approximately 5% included effector (CD44(high)CD62L(low)) and central (CD44(high)CD62L(high)) phenotype cells. Recall response was observed even at >300 days. CFSE-labeled naive OT-1 (OVA(257-264) TCR transgenic) cells transferred into MS-OVA-immunized recipients cycled profoundly (>90%) within the first week of immunization indicating potent Ag presentation. Moreover, approximately 25% cycling of Ag-specific cells was seen for >50 days, suggesting an Ag depot. In vivo, CD8(+) T cells evoked by MS-OVA killed >80% of specific targets, even at day 180. MS-OVA induced responses similar in magnitude to Listeria monocytogenes-OVA, a potent live vector. Furthermore, protective CD8(+) T cells were induced in TLR2-deficient mice, suggesting nonengagement of TLR2 by archaeal lipids. Thus, an archaeosome adjuvant vaccine represents an alternative to live vectors for inducing CD8(+) T cell memory.
Mesh Headings (Keywords): Adjuvants, Immunologic, Animals, Antigen Presentation, Antigens, CD44, CD8-Positive T-Lymphocytes, Female, Immunologic Memory, L-Selectin, Listeria monocytogenes, Methanobrevibacter, Mice, Mice, Knockout, Ovalbumin, Receptors, Interleukin-7, Time Factors, Toll-Like Receptor 2
Check for Full Text / PubMed Unique Identifier (PMID): 17277146
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