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Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse.

Bajénoff M, Narni-Mancinelli E, Brau F, Lauvau G - PLoS ONE (2010)

Bottom Line: Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens.Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing.Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale Unité 924, Groupe Avenir, Valbonne, France. bajenoff@ciml.univ-mrs.fr

ABSTRACT
Memory CD8(+) T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m). Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+) T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs) fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m) as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+) T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+) T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+) T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+) T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells.

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Related in: MedlinePlus

L.m-specific memory CD8+ T cells present in follicles are adjacent to reticular fibers.200 naïve GFP+ OT-I cells were transferred in C57BL/6 mice that were injected i.v. the following day with 0.1×LD50 Wt L.m-OVA. Spleens were harvested 30 days later, sectioned, stained for B220, CD3, collagen IV expression and analyzed by confocal microscopy. Inserts show enlargements of B220+ areas containing OT-I memory cells. Data are representative of 2 different experiments.
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pone-0011524-g003: L.m-specific memory CD8+ T cells present in follicles are adjacent to reticular fibers.200 naïve GFP+ OT-I cells were transferred in C57BL/6 mice that were injected i.v. the following day with 0.1×LD50 Wt L.m-OVA. Spleens were harvested 30 days later, sectioned, stained for B220, CD3, collagen IV expression and analyzed by confocal microscopy. Inserts show enlargements of B220+ areas containing OT-I memory cells. Data are representative of 2 different experiments.

Mentions: Because memory OT-I cells have been reported to home to B cell follicles, we focused on OT-I cells that were present in these zones [17]. We observed that follicular OT-I cells were in contact with adjacent collagen IV reticular fibers, suggesting that at least some memory CD8+ T cells present in follicles are indeed patrolling “T cell zone embassies” created by residual FRCs (Figure 3). Collectively, our results suggest that the majority of L.m-specific memory CD8+ T cells remains in the RP on steady state.


Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse.

Bajénoff M, Narni-Mancinelli E, Brau F, Lauvau G - PLoS ONE (2010)

L.m-specific memory CD8+ T cells present in follicles are adjacent to reticular fibers.200 naïve GFP+ OT-I cells were transferred in C57BL/6 mice that were injected i.v. the following day with 0.1×LD50 Wt L.m-OVA. Spleens were harvested 30 days later, sectioned, stained for B220, CD3, collagen IV expression and analyzed by confocal microscopy. Inserts show enlargements of B220+ areas containing OT-I memory cells. Data are representative of 2 different experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902518&req=5

pone-0011524-g003: L.m-specific memory CD8+ T cells present in follicles are adjacent to reticular fibers.200 naïve GFP+ OT-I cells were transferred in C57BL/6 mice that were injected i.v. the following day with 0.1×LD50 Wt L.m-OVA. Spleens were harvested 30 days later, sectioned, stained for B220, CD3, collagen IV expression and analyzed by confocal microscopy. Inserts show enlargements of B220+ areas containing OT-I memory cells. Data are representative of 2 different experiments.
Mentions: Because memory OT-I cells have been reported to home to B cell follicles, we focused on OT-I cells that were present in these zones [17]. We observed that follicular OT-I cells were in contact with adjacent collagen IV reticular fibers, suggesting that at least some memory CD8+ T cells present in follicles are indeed patrolling “T cell zone embassies” created by residual FRCs (Figure 3). Collectively, our results suggest that the majority of L.m-specific memory CD8+ T cells remains in the RP on steady state.

Bottom Line: Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens.Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing.Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale Unité 924, Groupe Avenir, Valbonne, France. bajenoff@ciml.univ-mrs.fr

ABSTRACT
Memory CD8(+) T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m). Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+) T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs) fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m) as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+) T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+) T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+) T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+) T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells.

Show MeSH
Related in: MedlinePlus