Cutting Edge: Resident Memory CD8 T Cells Occupy Frontline Niches in Secondary Lymphoid Organs

Jason M. Schenkel, Kathryn A. Fraser and David Masopust
J Immunol April 1, 2014, 192 (7) 2961-2964; DOI: https://doi.org/10.4049/jimmunol.1400003

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    A subset of memory CD8 T cells in SLO phenotypically resembles TRM. (A) Eight weeks after LCMV infection, P14 memory CD8 T cells in spleen were analyzed for the indicated markers by flow cytometry. All plots gated on Thy1.1+ P14 memory CD8 T cells. (B) As in (A), however, P14 splenocytes were split into CD69+ CD62L− (black line), CD69− CD62L− (blue line), and CD69− CD62L+ (red line) subsets. P14, isolated from small intestinal epithelium (green line), were included as a positive control for previously defined TRM. (C) P14 splenocyte phenotype was compared on days 7 and 40 after LCMV infection. (D) A total of 5 × 104 naive CD45.2+ OT-I splenocytes were transferred to CD45.1+ RAG−/− C57BL/6 mice. Sixty days later, OT-I splenocytes were analyzed for the indicated markers by flow cytometry. Data are representative of six mice from two independent experiments.

  • FIGURE 2.
    FIGURE 2.

    CD69+ SLO memory CD8 T cells are TRM positioned at common Ag entry sites. (A) P14 LCMV-immune chimeric (black bars) and naive (white bars) mice were surgically conjoined. Fifteen days later, the fraction of P14 that expressed CD69 was enumerated histologically within the SLO of both parabionts. (B) The proportion of CD69+ P14 (black) and CD69− P14 (white) memory CD8 T cells present in each SLO subcompartment of the immune parabiont was determined histologically. (C) Representative staining showing CD69+ memory CD8 T cells in the LN sinus. Scale bars, 20 μm. (D) Representative CD69 staining in the red pulp, white pulp, and marginal zone of the spleen. Original magnification ×20, (C) and (D). Scale bars in (D), 20 μm. (E) The fraction of P14 memory CD8 T cells within each SLO compartment of the immune parabiont that expressed CD69. Data are from six mice from two independent experiments. *p < 0.01, **p < 0.001.

  • FIGURE 3.
    FIGURE 3.

    Reduced IL-15 dependence of CD8 TRM in SLO. (A) CD122 (IL-15Rβ) expression was analyzed by flow cytometry on CD69+ (black line) and CD69− (gray line) memory P14 CD8 T cells isolated from spleen 60 d after LCMV infection. (B and C) P14 immune chimeras were generated in wild-type (WT; black) and IL-15−/− (white) mice. Sixty days later, CD69+ and CD69− P14 were enumerated in LN and spleen. Data are from five mice/group from two independent experiments representative of four different experiments. *p < 0.05, **p < 0.01, ***p < 0.001.

  • FIGURE 4.
    FIGURE 4.

    SLO TRM do not redistribute in response to peripheral inflammation. Both P14 and OT-I memory CD8 T cells were established in mice following LCMV and VSV-OVA infection. Mice were rechallenged transcervically with 50 μg gp33 peptide. Two days later, CD69− (left panel) and CD69+ (right panel) OT-I memory CD8 T cells were enumerated within spleen. Data are from three mice/group representative of two independent experiments. *p < 0.01.

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