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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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Memory CD8 T cells rapidly control secondary L.m infection.Mice (3 per group) were infected i.v with PBS or immunized with 0.1×LD50 Wt L.m bacteria. 30 days later, animals were injected or not with 100 µg of anti-CD8β depleting Ab i.p for three consecutive days and then challenged with 7×105 Wt bacteria. Bacteria titers in the spleen were measured 3, 6, 24 and 48 hours later. Data are representative of 2 independent experiments.
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pone-0011524-g001: Memory CD8 T cells rapidly control secondary L.m infection.Mice (3 per group) were infected i.v with PBS or immunized with 0.1×LD50 Wt L.m bacteria. 30 days later, animals were injected or not with 100 µg of anti-CD8β depleting Ab i.p for three consecutive days and then challenged with 7×105 Wt bacteria. Bacteria titers in the spleen were measured 3, 6, 24 and 48 hours later. Data are representative of 2 independent experiments.

Mentions: To accurately determine when memory CD8+ T cells start controlling L.m growth during a secondary infection, we injected mice intravenously (i.v) with PBS or 0.1×LD50 Wt bacteria (104) in order to induce a protective CD8 memory response. One month later, CD8+ T cells were eliminated or not with a depleting anti-CD8β treatment and mice were challenged with 10×LD50 Wt bacteria. Bacterial growth inside infected spleens was then monitored 3, 6, 24 and 48 hours following infection. As expected, immunized mice controlled the infection while CD8-depleted and PBS-injected animals exhibited at least 1000 fold more bacteria 24 hours after the challenge infection (Figure 1). Most interestingly, the control of L.m growth by memory CD8+ T cells was already visible after 6 hours, suggesting that memory cells not only had seen their cognate antigen at that time but had also started to kill bacteria inside infected spleens.


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)

Memory CD8 T cells rapidly control secondary L.m infection.Mice (3 per group) were infected i.v with PBS or immunized with 0.1×LD50 Wt L.m bacteria. 30 days later, animals were injected or not with 100 µg of anti-CD8β depleting Ab i.p for three consecutive days and then challenged with 7×105 Wt bacteria. Bacteria titers in the spleen were measured 3, 6, 24 and 48 hours later. Data are representative of 2 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0011524-g001: Memory CD8 T cells rapidly control secondary L.m infection.Mice (3 per group) were infected i.v with PBS or immunized with 0.1×LD50 Wt L.m bacteria. 30 days later, animals were injected or not with 100 µg of anti-CD8β depleting Ab i.p for three consecutive days and then challenged with 7×105 Wt bacteria. Bacteria titers in the spleen were measured 3, 6, 24 and 48 hours later. Data are representative of 2 independent experiments.
Mentions: To accurately determine when memory CD8+ T cells start controlling L.m growth during a secondary infection, we injected mice intravenously (i.v) with PBS or 0.1×LD50 Wt bacteria (104) in order to induce a protective CD8 memory response. One month later, CD8+ T cells were eliminated or not with a depleting anti-CD8β treatment and mice were challenged with 10×LD50 Wt bacteria. Bacterial growth inside infected spleens was then monitored 3, 6, 24 and 48 hours following infection. As expected, immunized mice controlled the infection while CD8-depleted and PBS-injected animals exhibited at least 1000 fold more bacteria 24 hours after the challenge infection (Figure 1). Most interestingly, the control of L.m growth by memory CD8+ T cells was already visible after 6 hours, suggesting that memory cells not only had seen their cognate antigen at that time but had also started to kill bacteria inside infected spleens.

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