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

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-2KbOVA257–264-specific CD8+ T cells declined by 14–21 days, and <1% of primarily central phenotype (CD44highCD62Lhigh) cells persisted. A booster injection of MS-OVA at 3–11 wk promoted massive clonal expansion and a peak effector response of ∼20% splenic/blood OVA257–264-specific CD8+ T cells. Furthermore, contraction was protracted and the memory pool (IL-7Rαhigh) of ∼5% included effector (CD44highCD62Llow) and central (CD44highCD62Lhigh) phenotype cells. Recall response was observed even at >300 days. CFSE-labeled naive OT-1 (OVA257–264 TCR transgenic) cells transferred into MS-OVA-immunized recipients cycled profoundly (>90%) within the first week of immunization indicating potent Ag presentation. Moreover, ∼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.

AsopBDeletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live AttenuatedSalmonella entericaVaccines

“…* , compared to 9241(pYA3634)-immunized mice, the P value was Ͻ0.05; ** , compared to 9241(pYA3634)-immunized mice, the P value was Ͻ0.01. (25). Therefore, we evaluated the effect of ⌬sopB on the stimulation of a memory T-cell response.…”

Involvement of CD8+ T cells in protective immunity against murine blood‐stage infection with Plasmodium yoelii 17XL strain

“…Naive T cells express CD62L (L-selectin), which is known to be a homing receptor, and shed this molecule to migrate from lymphoid organs to inflammatory sites after activation [18]. CD44 appears to be the most reliable marker that is expressed at high levels in all memory T cells of mice, irrespective of their activation status [19]. CD8 1 T cells can be classified into three groups according to their expression patterns of CD62L and CD44: CD62L hi CD44 lo , CD62L hi CD44 hi and CD62L lo CD44 hi patterns represent naive, central memory, and effector memory phenotypes, respectively [19].…”

“…CD44 appears to be the most reliable marker that is expressed at high levels in all memory T cells of mice, irrespective of their activation status [19]. CD8 1 T cells can be classified into three groups according to their expression patterns of CD62L and CD44: CD62L hi CD44 lo , CD62L hi CD44 hi and CD62L lo CD44 hi patterns represent naive, central memory, and effector memory phenotypes, respectively [19]. Spleen cells from recipient mice transferred with the indicated cells were analyzed 7 days after infection with PyL ( Fig.…”

Lymphotoxin-α and TNF Have Essential but Independent Roles in the Evolution of the Granulomatous Response in Experimental Leprosy

“…Although the repertoire of T cell activation markers is rapidly expanding, 30 the relative levels of CD44 and CD62L are frequently used to distinguish naïve (CD44 lo CD62L hi ) from effector (CD44 hi CD62L lo ) T cells. [31][32][33][34][35][36][37] In the M. leprae-infected FPs, the majority of CD4 ϩ and CD8 ϩ cells were of the effector phenotype, expressing CD44 hi CD62L lo (87.77 Ϯ 1.62% and 82.76 Ϯ 1.93, respectively). We also attempted to evaluate the cellular composition of the cLT␣ Ϫ/Ϫ FPs by flow cytometry; however, we were unsuccessful as these preparations lacked sufficient numbers of leukocytes for a reliable assessment.…”