IL-15R alpha expression on CD8+ T cells is dispensable for T cell memory - PubMed (original) (raw)

IL-15R alpha expression on CD8+ T cells is dispensable for T cell memory

Patrick R Burkett et al. Proc Natl Acad Sci U S A. 2003.

Abstract

The generation and maintenance of immunological memory requires the activation, expansion, and persistent proliferation of antigen-specific T cells. Recent work suggests that IL-15 may be important for this process. Surprisingly, we now find that expression of the high-affinity receptor for IL-15, IL-15R alpha, on T cells is dispensable for the generation or maintenance of memory CD8(+) T cells. By contrast, IL-15R alpha expression on cells other than T cells is absolutely critical for this function. These findings may be related to IL-15R alpha's ability to present IL-15 in trans to low-affinity IL-15R beta gamma(c) receptors on memory CD8(+) T cells. These unexpected results provide insights into how IL-15R alpha supports memory CD8(+) T cells.

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Figures

Figure 1

Figure 1

IL-15Rα expression on CD8+ T cells is dispensable for CD8+ T cell memory. Similar percentages of IL-15Rα+/− (■) and IL-15Rα−/− (□) OT-1+ RAG−/− CD8+ T cells at memory time points in the PBL. Data represent the mean of four mice per time point ± SEM.

Figure 2

Figure 2

Naïve IL-15Rα-competent CD8+ T cells show normal short-term maintenance and initial expansion in response to either OVA or OVA plus poly(I⋅C) in both IL-15Rα+/− and IL-15Rα−/− mice. There were similar percentages of H2Kb-OVA+ CD8+ cells in the peripheral lymph nodes (PLNs) 4 days after immunization in both IL-15Rα+/− and IL-15Rα−/− mice. Plots are representative of at least two mice per condition. Data represent mean ± SEM.

Figure 3

Figure 3

IL-15Rα−/− mice fail to support IL-15Rα-competent memory CD8+ T cells, despite normal initial responses. (A) Percentages of H2Kb-OVA+ in the PLN, PBL, liver, and lamina propria lymphocytes (LPLs) of IL-15Rα+/− (filled squares or bars) or IL-15Rα−/− mice (open squares or bars) at various time points following immunization with OVA and poly(I⋅C). (B) Percentages of IFN-γ+ CD8+ T cells are shown in the PLN and spleen of IL-15Rα+/− (filled squares) or IL-15Rα−/− mice (open squares) at various time points after immunization with OVA and poly(I⋅C). Data represent mean ± SEM and all data points are reflective of at least two mice, with most reflecting three or more mice.

Figure 4

Figure 4

IL-15Rα−/− mice fail to properly maintain IL-15Ra+/− memory CD8+ T cells. (A) Reduced numbers of IFN-γ+ IL-15Rα+/− memory CD8+ T cells are recovered from IL-15Rα−/− mice 110 days after secondary transfer. The mean total number of Ly5.1+ IFN-γ+ cells recovered from both spleen and lymph nodes are shown ± SEM. Data represent three mice. (B) IL-15Rα+/− memory CD8+ T cells undergo reduced proliferation 55 days after secondary transfer into IL-15Rα−/− hosts. FACS plots are representative of at least two mice. Plots are gated on Ly5.1+ CD8+ T cells and the percentage in each generation is indicated.

Figure 5

Figure 5

IL-15Rα expression on both radiation-sensitive and radiation-resistant cells maintains memory CD8+ T cells. IL-15Rα+/+ (filled squares or triangles) or IL-15Rα−/− (open squares or triangles) mice were lethally irradiated and reconstituted with either IL-15Rα+/− (squares) or IL-15Rα−/− (triangles) bone marrow. At least 4 months after irradiation, mice received OT-1+ RAG−/− CD8+ T cells, and were immunized with OVA and poly(I⋅C). Data represent mean ± SEM of PBLs from at least two mice per group, with most reflecting three or more mice.

Figure 6

Figure 6

Trans presentation of IL-15 by IL-15Rα can support memory CD8+ T cell survival in vitro. (A) IL-15 presented in trans by IL-15Rα supports T cell viability in vitro. The number of viable cells after 4 days is reported as a percentage of total collected events. (B) IL-15 presented in trans by IL-15Rα selectively supports memory phenotype CD8+ T cells. The percentage of total viable cells that are CD44Hi CD8+ T cells after 4 days of culture is indicated. (C) IL-15Rα-bound IL-15 comparably supports both IL-15Rα+/− and IL-15Rα−/− memory OT-1+ RAG−/− CD8+ T cells in vitro. T cells were purified from WT mice that had received either IL-15Rα+/− or IL-15Rα−/− OT-1+ RAG−/− CD8+ T cells and been immunized with poly(I⋅C) and OVA 40 days before isolation. The percentage of total viable cells that are memory OT-1+ CD8+ T cells after 4 days in culture is indicated. The bars labeled Input reflect the percentage of such cells before culture. This experiment was performed three times with similar results.

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