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Splenectomy Alters Distribution and Turnover but not Numbers or Protective Capacity of de novo Generated Memory CD8 T-Cells.

Kim MT, Harty JT - Front Immunol (2014)

Bottom Line: Using TCR-transgenic P14 cells, we demonstrate that homeostatic proliferation and representation of pathogen-specific memory CD8 T-cells in the blood are enhanced in splenectomized compared to sham surgery mice.Surprisingly, despite the enhanced turnover, splx mice displayed no changes in total memory CD8 T-cell numbers nor impaired protection against lethal dose challenge with Listeria monocytogenes.Thus, our data suggest that memory CD8 T-cell maintenance and function remain intact in the absence of the spleen.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA , USA.

ABSTRACT
The spleen is a highly compartmentalized lymphoid organ that allows for efficient antigen presentation and activation of immune responses. Additionally, the spleen itself functions to remove senescent red blood cells, filter bacteria, and sequester platelets. Splenectomy, commonly performed after blunt force trauma or splenomegaly, has been shown to increase risk of certain bacterial and parasitic infections years after removal of the spleen. Although previous studies report defects in memory B-cells and IgM titers in splenectomized patients, the effect of splenectomy on CD8 T-cell responses and memory CD8 T-cell function remains ill defined. Using TCR-transgenic P14 cells, we demonstrate that homeostatic proliferation and representation of pathogen-specific memory CD8 T-cells in the blood are enhanced in splenectomized compared to sham surgery mice. Surprisingly, despite the enhanced turnover, splx mice displayed no changes in total memory CD8 T-cell numbers nor impaired protection against lethal dose challenge with Listeria monocytogenes. Thus, our data suggest that memory CD8 T-cell maintenance and function remain intact in the absence of the spleen.

No MeSH data available.


Related in: MedlinePlus

Protective capacity of memory CD8 T-cells unaltered in the absence of spleen. Sham and splx-treated mice were infected i.p. with 2 × 105 PFU LCMV-Armstrong on D-6 and D-15. Naïve P14 CD8 T-cells were labeled with CFSE and adoptively transferred into infected mice at D0 (2 × 106/mouse). Inguinal lymph nodes were harvested 3 days post-transfer and analyzed for CFSE dilution. (A) CFSE dilution of P14 cells from inguinal lymph nodes. (B) Naïve B6 mice and memory P14 sham and splx-treated mice were challenged with 1 × 106 CFU virulent LM-gp33 (XFL203) intravenously. Bacterial burden in the liver was assessed on D3 post-challenge. (C) Frequency of IFNγ positive P14 cells in sham and splx mice. Data are represented as mean ± S.D. with five or more mice per group. ***p < 0.0005.
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Figure 5: Protective capacity of memory CD8 T-cells unaltered in the absence of spleen. Sham and splx-treated mice were infected i.p. with 2 × 105 PFU LCMV-Armstrong on D-6 and D-15. Naïve P14 CD8 T-cells were labeled with CFSE and adoptively transferred into infected mice at D0 (2 × 106/mouse). Inguinal lymph nodes were harvested 3 days post-transfer and analyzed for CFSE dilution. (A) CFSE dilution of P14 cells from inguinal lymph nodes. (B) Naïve B6 mice and memory P14 sham and splx-treated mice were challenged with 1 × 106 CFU virulent LM-gp33 (XFL203) intravenously. Bacterial burden in the liver was assessed on D3 post-challenge. (C) Frequency of IFNγ positive P14 cells in sham and splx mice. Data are represented as mean ± S.D. with five or more mice per group. ***p < 0.0005.

Mentions: As numbers and subsets of memory CD8 T-cells are similar among sham and splx mice, we next investigated the functionality of these cells in either environment. First, we tested the ability of memory CD8 T-cells to clear LCMV-Armstrong in sham and splx mice. To do this, we infected sham and splx mice with LCMV-Armstrong at D-6 and D-15 with subsequent transfer of CFSE-labeled naïve CD8 T-cells on D0 to detect functional antigen display as a measure of antigen clearance. P14 CD8 T-cells from both groups of mice underwent similar division at D6 post-infection with essentially no division at D15 post-infection (Figure 5A). Thus, sham and splx mice had the same capacity to clear LCMV antigen. We next assessed protective capacity of memory CD8 T-cells in sham and splx mice via lethal infection with virulent L. monocytogenes. Naïve or memory P14 sham and splx mice were challenged with a high dose (1 × 106 CFU) of virulent LM-gp33 intravenously. Both sham and splx mice reduced CFU of LM-gp33 in the liver 3 days post-infection by 4 logs compared to naïve controls (Figure 5B). Additionally, there was no significant difference in protective capacity between sham and splx mice. Finally, we assessed IFNγ production from memory CD8 T-cells in sham and splx mice. Across multiple tissue compartments, there was no significant difference in cytokine production between memory CD8 T-cells in a splx compared to sham host (Figure 5C).


Splenectomy Alters Distribution and Turnover but not Numbers or Protective Capacity of de novo Generated Memory CD8 T-Cells.

Kim MT, Harty JT - Front Immunol (2014)

Protective capacity of memory CD8 T-cells unaltered in the absence of spleen. Sham and splx-treated mice were infected i.p. with 2 × 105 PFU LCMV-Armstrong on D-6 and D-15. Naïve P14 CD8 T-cells were labeled with CFSE and adoptively transferred into infected mice at D0 (2 × 106/mouse). Inguinal lymph nodes were harvested 3 days post-transfer and analyzed for CFSE dilution. (A) CFSE dilution of P14 cells from inguinal lymph nodes. (B) Naïve B6 mice and memory P14 sham and splx-treated mice were challenged with 1 × 106 CFU virulent LM-gp33 (XFL203) intravenously. Bacterial burden in the liver was assessed on D3 post-challenge. (C) Frequency of IFNγ positive P14 cells in sham and splx mice. Data are represented as mean ± S.D. with five or more mice per group. ***p < 0.0005.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4222231&req=5

Figure 5: Protective capacity of memory CD8 T-cells unaltered in the absence of spleen. Sham and splx-treated mice were infected i.p. with 2 × 105 PFU LCMV-Armstrong on D-6 and D-15. Naïve P14 CD8 T-cells were labeled with CFSE and adoptively transferred into infected mice at D0 (2 × 106/mouse). Inguinal lymph nodes were harvested 3 days post-transfer and analyzed for CFSE dilution. (A) CFSE dilution of P14 cells from inguinal lymph nodes. (B) Naïve B6 mice and memory P14 sham and splx-treated mice were challenged with 1 × 106 CFU virulent LM-gp33 (XFL203) intravenously. Bacterial burden in the liver was assessed on D3 post-challenge. (C) Frequency of IFNγ positive P14 cells in sham and splx mice. Data are represented as mean ± S.D. with five or more mice per group. ***p < 0.0005.
Mentions: As numbers and subsets of memory CD8 T-cells are similar among sham and splx mice, we next investigated the functionality of these cells in either environment. First, we tested the ability of memory CD8 T-cells to clear LCMV-Armstrong in sham and splx mice. To do this, we infected sham and splx mice with LCMV-Armstrong at D-6 and D-15 with subsequent transfer of CFSE-labeled naïve CD8 T-cells on D0 to detect functional antigen display as a measure of antigen clearance. P14 CD8 T-cells from both groups of mice underwent similar division at D6 post-infection with essentially no division at D15 post-infection (Figure 5A). Thus, sham and splx mice had the same capacity to clear LCMV antigen. We next assessed protective capacity of memory CD8 T-cells in sham and splx mice via lethal infection with virulent L. monocytogenes. Naïve or memory P14 sham and splx mice were challenged with a high dose (1 × 106 CFU) of virulent LM-gp33 intravenously. Both sham and splx mice reduced CFU of LM-gp33 in the liver 3 days post-infection by 4 logs compared to naïve controls (Figure 5B). Additionally, there was no significant difference in protective capacity between sham and splx mice. Finally, we assessed IFNγ production from memory CD8 T-cells in sham and splx mice. Across multiple tissue compartments, there was no significant difference in cytokine production between memory CD8 T-cells in a splx compared to sham host (Figure 5C).

Bottom Line: Using TCR-transgenic P14 cells, we demonstrate that homeostatic proliferation and representation of pathogen-specific memory CD8 T-cells in the blood are enhanced in splenectomized compared to sham surgery mice.Surprisingly, despite the enhanced turnover, splx mice displayed no changes in total memory CD8 T-cell numbers nor impaired protection against lethal dose challenge with Listeria monocytogenes.Thus, our data suggest that memory CD8 T-cell maintenance and function remain intact in the absence of the spleen.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Program in Immunology, University of Iowa , Iowa City, IA , USA.

ABSTRACT
The spleen is a highly compartmentalized lymphoid organ that allows for efficient antigen presentation and activation of immune responses. Additionally, the spleen itself functions to remove senescent red blood cells, filter bacteria, and sequester platelets. Splenectomy, commonly performed after blunt force trauma or splenomegaly, has been shown to increase risk of certain bacterial and parasitic infections years after removal of the spleen. Although previous studies report defects in memory B-cells and IgM titers in splenectomized patients, the effect of splenectomy on CD8 T-cell responses and memory CD8 T-cell function remains ill defined. Using TCR-transgenic P14 cells, we demonstrate that homeostatic proliferation and representation of pathogen-specific memory CD8 T-cells in the blood are enhanced in splenectomized compared to sham surgery mice. Surprisingly, despite the enhanced turnover, splx mice displayed no changes in total memory CD8 T-cell numbers nor impaired protection against lethal dose challenge with Listeria monocytogenes. Thus, our data suggest that memory CD8 T-cell maintenance and function remain intact in the absence of the spleen.

No MeSH data available.


Related in: MedlinePlus