Early commitment of adoptively transferred CD4+ T cells following particle-mediated DNA vaccination: implications for the study of immunomodulation

Creusot, Rémi J.; Thomsen, Lindy L.; Wely, Cathy A. van; Topley, Peter; Tite, J P; Chain, Benjamin M.

doi:10.1016/s0264-410x(00)00405-9

Cited by 16 publications

(13 citation statements)

References 44 publications

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“…For mice immunized with the pVAC1 empty vector, very few cells (<0·5%) had undergone clonal expansion in vivo ; the expression of CD69 was similar to pVAC1.OVA‐immunized mice, but no cytokines were detected following in vitro restimulation with peptide, which is consistent with previously published data for this model 20 …”

Section: Resultssupporting

confidence: 89%

“…5), suggesting that that the majority of cells in the lymph nodes had been speci®cally activated in vivo. Some cells also showed high expression of the CD69 activation marker, as has been observed previously in this model, 20 although this was downregulated in cells that had undergone cell divisions (Fig. 5).…”

Section: Only a Proportion Of Primary Effector Cd4 T Cells That Have supporting

confidence: 83%

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Characterization of CC‐chemokine receptor 7 expression on murine T cells in lymphoid tissues

et al. 2003

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Summary Expression of the lymph node homing and CC‐chemokine receptor 7 (CCR7), with L‐selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 and used this antibody to study CCR7 expression on murine T‐cell subsets. Using flow cytometric staining of T cells for visualisation expression of CCR7 in association with CD62L and CD44, a major population of CD4 or CD8 T cells expressing CCR7 were found to be CD62Lhigh CD44low, which would suggest a naïve cell phenotype. By analogy with human studies, memory cells could be subdivided into CCR7high CD62Lhigh CD44high (central memory) and CCR7low CD62Llow CD44high (effector memory). The proportions of these populations were different in lymph node, blood and spleen. Functional, short‐term in vitro polyclonal stimulation of blood, spleen and lymph node cells from naive mice demonstrated that CCR7high CD4 T cells produced predominantly interleukin (IL)‐2, whereas CCR7low CD4 T cells produced both IL‐2 and interferon‐γ (IFN‐γ). However, in contrast to previously published reports, the CCR7high CD8 T‐cell subpopulation produced both IFN‐γ and IL‐2. Analysis of effector T cells, induced by immunization in vivo, showed that a proportion of activated naïve CD4 T cells down‐regulated CCR7 only after multiple cell divisions, and this coincided with the down‐regulation of CD62L and production of IL‐4 and IFN‐γ. Finally, analysis of effector T cells during the phase of maximal clonal expansion of secondary immune responses in vivo indicated that the vast majority of both IL‐2‐ and IFN‐γ‐producing cells are CCR7low, while few cytokine‐expressing CCR7high T cells were detected. Our results support the hypothesis, developed from studies with human cells, that CCR7 may separate functionally different murine memory T‐cell subpopulations, but indicate additional complexity in that CCR7high CD8 T cells also may produce IFN‐γ.

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Section: Resultssupporting

confidence: 89%

Section: Only a Proportion Of Primary Effector Cd4 T Cells That Have supporting

confidence: 83%

Characterization of CC‐chemokine receptor 7 expression on murine T cells in lymphoid tissues

et al. 2003

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“…Others have shown significant clonal expansion of DO11.10 T cells following gene gun immunization of OVA-expressing plasmids (33). In contrast, we were unable to demonstrate significant and reproducible increases in the total percentage of DO11.10 cells in the draining lymph nodes, although we could identify individual mice that had elevated numbers of Tg T cells.…”

Section: Discussioncontrasting

confidence: 91%

Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways

Rush

Mitchell

Garside

2002

The Journal of Immunology

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The initial cellular events and interactions that occur following DNA immunization are likely to be key to determining the character and magnitude of the resulting immune response, and as such, a better understanding of these events could ultimately lead to the design of more effective pathogen-appropriate DNA vaccines. Therefore, we have used a variety of sensitive cell-based techniques to study the induction of adaptive immunity in vivo. We examined the efficacy of induction of Ag-specific CD4+ and CD8+ T cell responses in vivo by the adoptive transfer of fluorescently labeled Ag-specific TCR transgenic T cells and have demonstrated how such approaches can be used to study the effect of simple DNA construct manipulations on immunological priming. OVA-specific CD8+ and CD4+ T cells were activated and divided in vivo following immunization with DNA constructs that targeted OVA expression to different subcellular locations; however, the kinetics and degree of cell proliferation were dependent on the cellular location of the expressed protein. DNA vectors encoding cell-associated OVA resulted in greater CD8+ T cell division compared with other forms of OVA. In contrast, soluble secreted OVA targeted to the classical secretory pathway enhanced division of CD4+ T cells. Furthermore, the inclusion of mammalian introns to enhance protein expression increased the ability of poorly immunogenic forms of Ag to activate naive T cells, indicating that not only the location, but also the amount of Ag expression, is important for efficient T cell priming following DNA injection.

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“…Limiting Ag expression to cells with such a rare frequency was insufficient to trigger efficient CD4 or CD8 T cell responses as measured with highly sensitive adoptive transfer methods. Although we could reproduce the previously reported (38) clonal expansion kinetics and magnitude of DO11.10 T cells upon gene gun immunization with CMV promoter-driven constructs, all CD11c-driven vaccines failed to do so. In contrast, CD11c-driven constructs could elicit Ab responses comparable to those observed with ubiquitously active CMV promoter constructs (Fig.…”

Section: Discussionmentioning

confidence: 62%

Insufficient APC Capacities of Dendritic Cells in Gene Gun-Mediated DNA Vaccination

Lauterbach

Gruber

Ried

et al. 2006

The Journal of Immunology

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Gene gun-mediated DNA immunization is a powerful mode of vaccination against infectious diseases and tumors. Many studies have identified dendritic cells (DC) as the central players in inducing immunity upon biolistic DNA vaccination; however, none of these studies directly quantify DC-mediated responses in comparison with immunity triggered by all Ag- and MHC-expressing cells. In this study we use two different approaches to decipher the relative role of DC vs other cell types in gene gun-induced immunity. First, we directly compared the immunization efficacy of different DNA constructs, which allow Ag expression ubiquitously (CMV promoter) or specifically in DC (CD11c promoter) and would encode either for soluble or membrane bound forms of Ag. Second, we immunized transgenic mice in which only DC can present MHC-restricted Ag, and directly compared the magnitudes of CTL activation with those obtained in wild-type mice. Surprisingly, our combined data suggest that, although DC-specific Ag expression is sufficient to induce humoral responses, DC alone cannot trigger optimal CD4 and CD8 T cell responses upon gene gun vaccination. Therefore, we conclude that DC alone are insufficient to mediate optimal induction of T cell immunity upon gene gun DNA vaccination and that broad Ag expression rather than DC-restricted approaches are necessary for induction of complete immune responses.

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Early commitment of adoptively transferred CD4+ T cells following particle-mediated DNA vaccination: implications for the study of immunomodulation

Cited by 16 publications

References 44 publications

Characterization of CC‐chemokine receptor 7 expression on murine T cells in lymphoid tissues

Characterization of CC‐chemokine receptor 7 expression on murine T cells in lymphoid tissues

Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways

Insufficient APC Capacities of Dendritic Cells in Gene Gun-Mediated DNA Vaccination

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