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Cutting Edge: Requirement for IL-15 in the Generation of Primary and Memory Antigen-Specific CD8 T Cells

Kimberly S. Schluns, Kristina Williams, Averil Ma, Xin X. Zheng and Leo Lefrançois
J Immunol May 15, 2002, 168 (10) 4827-4831; DOI: https://doi.org/10.4049/jimmunol.168.10.4827
Kimberly S. Schluns
*Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030;
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Kristina Williams
*Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030;
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Averil Ma
†Committee on Immunology, University of Chicago, Chicago, IL 60637; and
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Xin X. Zheng
‡Department of Medicine, Division of Immunology, Harvard Medical School, Boston, MA 02215
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Leo Lefrançois
*Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030;
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    FIGURE 1.

    IL-15 is required during the primary CD8 T cell response to VSV infection. A and B, Seven days after VSV infection, lymphocytes were isolated from spleen (SP), PLN, MLN, intestinal LP, lung (LG), and liver (LV) and analyzed for expression of CD8, CD44, and for reactivity with N-tetramer. Values represent percent tetramer-positive cells among CD8 T cells. B, Mean percent ± SD of N-tetramer-positive among CD8 T cells (n = 3). C, Percent tetramer-positive among CD8 T cells in peripheral blood. ∗, Significance of p < 0.05. Data are representative of three experiments.

  • FIGURE 2.
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    FIGURE 2.

    Primary expansion of virus-specific CD8 T cells does not require IL-15Rα. A and B, CD8 T cells 7 days postinfection. Values are percentage of tetramer-positive cells among CD8+ T cells. B, Mean percent ± SD of N-tetramer-positive CD8 T cells (n = 3–4). Data are representative of three experiments.

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    FIGURE 3.

    IL-15 and IL-15Rα are required for generation of normal numbers of antiviral memory CD8 T cells. A and C, Mean percent ± SD of tetramer-positive cells among CD8 T cells 38 days (A) and 75 days (C) after infection (n = 3). B and D, Different experiments showing percentage of tetramer-positive CD8 T cells in the peripheral blood. Numbers represent the percentage of control.

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    FIGURE 4.

    Proliferation of memory CD8 T cells is defective in IL-15−/− and IL-15R−/− mice. VSV-infected mice were given BrdU for 4 wk. A, BrdU intensity on N-tetramer-positive CD8+ gated cells. Splenocytes from VSV-infected mice were stained with CFSE and transferred into either control or IL-15−/− mice. B and C, CFSE intensity of total CD8 T cells (B) and N-tetramer-positive CD8+ gated T cells (C) 50 days after transfer. R is the calculated value of the percentage of the population responding.

  • FIGURE 5.
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    FIGURE 5.

    IL-15Rα is expressed on naive CD8 T cells and is up-regulated on effector and memory CD8 T cells. Spleen cells from unimmunized normal mice and VSV-infected normal and IL-15Rα−/− mice were incubated with IL-15/Fc followed by anti-IgG2a-PE Ab to detect binding. Panel 1, IL-15/Fc binding of CD8 T cells from unimmunized mice: control CD44high (shaded histogram), control CD44low cells (bold black line), and IL-15Rα−/− CD8+cells (thin black line). Panels 2 and 3, IL-15/Fc binding on N-tetramer-positive CD8 T cells 6 and 75 days postinfection: control mice (shaded histograms) and IL-15Rα−/− mice (bold thick histograms). The negative control represents staining in the absence of the IL-15/Fc but in the presence of the anti-IgG2a secondary Ab (panel 2, thin black line).

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The Journal of Immunology: 168 (10)
The Journal of Immunology
Vol. 168, Issue 10
15 May 2002
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Cutting Edge: Requirement for IL-15 in the Generation of Primary and Memory Antigen-Specific CD8 T Cells
Kimberly S. Schluns, Kristina Williams, Averil Ma, Xin X. Zheng, Leo Lefrançois
The Journal of Immunology May 15, 2002, 168 (10) 4827-4831; DOI: 10.4049/jimmunol.168.10.4827

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Cutting Edge: Requirement for IL-15 in the Generation of Primary and Memory Antigen-Specific CD8 T Cells
Kimberly S. Schluns, Kristina Williams, Averil Ma, Xin X. Zheng, Leo Lefrançois
The Journal of Immunology May 15, 2002, 168 (10) 4827-4831; DOI: 10.4049/jimmunol.168.10.4827
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