Compartmentalization of Bacterial Antigens: Differential Effects on Priming of CD8 T Cells and Protective Immunity

Shen, Hao; Miller, Jeff F.; Fan, Xueli; Kolwyck, David; Ahmed, Rafi; Harty, John T.

doi:10.1016/s0092-8674(00)80946-0

Cited by 212 publications

(188 citation statements)

References 47 publications

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“…The preferential priming of an Ag-specific CD8 T cell response by a secretory, but not cytoplasmic, Ag has also been demonstrated in the kinetoplastid T. cruzi and in Salmonella (12,13). However, both secreted and cytoplasmic Ags of Listeria monocytogenes were able to prime an Ag-specific CD8 T cell response (11). Therefore, the impact of the compartmentalization of an Ag on the induction of an Ag-specific CD8 T cell response is pathogen defined and may be dependent on the intracellular life cycle and survival strategy of the pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it is yet unresolved whether both secreted and cytoplasmic Ag of T. gondii induce a CD8 T cell response, although there is clear evidence that at least the tachyzoite-specific SAG1 protein, which is released from the cell surface of T. gondii, induces T. gondii-specific CD8 T cell responses (10). Previously, a systematic analysis on the role of Ag compartmentalization for the induction of CD8 T cells was successfully performed by the expression of a heterologous Ag under various experimental conditions in bacterial pathogens as well as in the protozoal kinetoplast Trypanosoma cruzi (11)(12)(13). These studies revealed that the compartmentalization of pathogen-derived Ag plays a decisive role for the resulting CD8 T cell response and that depending on the pathogen secreted, both secreted and cytoplasmic Ag elicit Ag-specific CD8 T cell responses.…”

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confidence: 99%

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The Induction and Kinetics of Antigen-Specific CD8 T Cells Are Defined by the Stage Specificity and Compartmentalization of the Antigen in Murine Toxoplasmosis

Kwok

Lütjen

Soltek

et al. 2003

The Journal of Immunology

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Toxoplasma gondii forms different life stages, fast-replicating tachyzoites and slow-growing bradyzoites, in mammalian hosts. CD8 T cells are of crucial importance in toxoplasmosis, but it is unknown which parasite stage is recognized by CD8 T cells. To analyze stage-specific CD8 T cell responses, we generated various recombinant Toxoplasma gondii expressing the heterologous Ag β-galactosidase (β-gal) and studied whether 1) secreted or cytoplasmic Ags and 2) tachyzoites or bradyzoites, which persist intracerebrally, induce CD8 T cells. We monitored the frequencies and kinetics of β-gal-specific CD8 T cells in infected mice by MHC class I tetramer staining. Upon oral infection of B6C (H-2bxd) mice, only β-gal-secreting tachyzoites induced β-gal-specific CD8 T cells. However, upon secondary infection of mice that had received a primary infection with tachyzoites secreting β-gal, β-gal-secreting tachyzoites and bradyzoites transiently increased the frequency of intracerebral β-gal-specific CD8 T cells. Frequencies of splenic and cerebral β-gal-specific CD8 T cells peaked at day 23 after infection, thereafter persisting at high levels in the brain but declining in the spleen. Splenic and cerebral β-gal-specific CD8 T cells produced IFN-γ and were cytolytic upon specific restimulation. Thus, compartmentalization and stage specificity of an Ag determine the induction of CD8 T cells in toxoplasmosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Induction and Kinetics of Antigen-Specific CD8 T Cells Are Defined by the Stage Specificity and Compartmentalization of the Antigen in Murine Toxoplasmosis

Kwok

Lütjen

Soltek

et al. 2003

The Journal of Immunology

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“…L. monocytogenes-specific memory T cells are very specific for the elimination of only bacteria that they can recognize and there is little bystander killing of nonrecognizable bacteria [70]. Memory T cell killing is also limited to the ability of the T cells to recognize all infected cells-if some infected cell subsets cannot present the recognized antigen, then memory T cells are not be able to adequately control infection [71,72]. In fact, perforin is perhaps the most important effector protein to provide protective immunity against L. monocytogenes.…”

Section: Cd4 and Cd8 T Cell Responsesmentioning

confidence: 99%

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Zenewicz

Shen

2007

Microbes and Infection

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177

172

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The Gram-positive facultative intracellular bacterium Listeria monocytogenes is a model pathogen for elucidating important mechanisms of the immune response. Infection of mice with a sub-lethal dose of bacteria generates highly reproducible innate and adaptive immune responses, resulting in clearance of the bacteria and resistance to subsequent L. monocytogenes infection. Both the innate and adaptive immune systems are crucial to the recognition and elimination of this pathogen from the host.

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“…As an indirect approach to address this issue, Shen et al constructed recombinant L. monocytogenes that expressed the LCMV nucleoprotein Ag as a secreted or non-secreted fusion protein [42]. Both forms of the Ag, either secreted into the host cell cytoplasm or retained within bacteria, efficiently primed CD8 + T cell responses.…”

Section: Which Apc Process L Monocytogenes Ag?mentioning

confidence: 99%

Mini‐review: Presentation of pathogen‐derived antigens in vivo

Lauvau

Glaichenhaus

2004

Eur J Immunol

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Most intracellular pathogens induce robust T cell responses upon infection of mammalian hosts. In most cases, these T cell responses are protective and result in pathogen clearance. It is therefore important to determine how T cells are primed and how they differentiate into cytokine-secreting and/or cytotoxic effector cells. In contrast to B cells, which recognize soluble Ag, CD8 + and CD4 + T cells react to Ag-derived peptides bound to MHC I or MHC II molecules, respectively. Therefore, elucidating the mechanisms by which pathogen-derived Ag become available for presentation is necessary to understand how pathogens trigger T cell responses in vivo. Although many excellent reviews have focused on the mechanisms involved in Ag processing, very few have pointed to the specificity of host-pathogen interactions. In this respect, it should be noticed that these interactions are very different from one pathogen to another, and may result in the involvement of different cells and molecules. Because of space limitations, we have decided to focus this review on two intracellular pathogens -vaccinia virus and Listeria monocytogenes. We have chosen these two pathogens because they both induce a strong CD8 + T cell response and because they have been extensively studied by both microbiologists and immunologists.

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Compartmentalization of Bacterial Antigens: Differential Effects on Priming of CD8 T Cells and Protective Immunity

Cited by 212 publications

References 47 publications

The Induction and Kinetics of Antigen-Specific CD8 T Cells Are Defined by the Stage Specificity and Compartmentalization of the Antigen in Murine Toxoplasmosis

The Induction and Kinetics of Antigen-Specific CD8 T Cells Are Defined by the Stage Specificity and Compartmentalization of the Antigen in Murine Toxoplasmosis

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Mini‐review: Presentation of pathogen‐derived antigens in vivo

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