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Biomedical subjects

Patrick R Burkett

Publications and source records attributed to Patrick R Burkett.

6 recordsLinked to original sources
PubMed2004

Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis.

The high affinity interleukin (IL)-15 receptor, IL-15Ralpha, is essential for supporting lymphoid homeostasis. To assess whether IL-15Ralpha's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Ralpha- and IL-2/15Rbeta-deficient mice. We find that IL-15Ralpha-competent, IL-2/15Rbeta-deficient cells are able to support IL-15Ralpha-deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Ralpha-mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Ralpha functions in vivo. Surprisingly, using IL-15- and IL-15Ralpha-deficient mixed chimera, we also find that IL-15 and IL-15Ralpha must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Ralpha is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Ralpha defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells.

Animals↗
PubMed2003

Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice.

Natural killer (NK) cells protect hosts against viral pathogens and transformed cells. IL-15 is thought to play a critical role in NK cell development, but its role in the regulation of peripheral NK cells is less well defined. We now find that adoptive transfer of normal NK cells into mice lacking the high affinity interleukin (IL)-15 receptor, IL-15Ralpha, surprisingly results in the abrupt loss of these cells. Moreover, IL-15Ralpha-deficient NK cells can differentiate successfully in radiation bone marrow chimera bearing normal cells. Finally, adoptively transferred IL-15Ralpha-deficient NK cells survive in normal but not IL-15Ralpha-deficient mice. These findings demonstrate that NK cell-independent IL-15Ralpha expression is critical for maintaining peripheral NK cells, while IL-15Ralpha expression on NK cells is not required for this function.

Adoptive Transfer↗
PubMed2003

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

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.

Adjuvants, Immunologic↗
PubMed2002

Regulation of lymphoid homeostasis by interleukin-15.

Interleukin (IL)-15 is a member of the common gamma chain family of cytokines, and is closely related to IL-2. While these two cytokines share several important biological functions in vitro, recent mouse models have demonstrated unique roles for these two cytokines in supporting lymphoid homeostasis in vivo. IL-15 has been shown to regulate the homeostasis of both innate and adaptive immune cells, and this review will discuss several ways in which this pleiotropic cytokine may support lymphoid homeostasis.

Animals↗