Interleukin-15 up-regulates interleukin-2 receptor alpha chain but down-regulates its own high-affinity binding sites on human T and B cells.
The cytokines interleukin (IL)-2 and IL-15 share many biological activities as a consequence of their utilization of the beta and gamma chains of the IL-2 receptor. However, each cytokine binds to a specific receptor alpha chain; IL-2 with low affinity and IL-15 with high affinity. Here, we demonstrate that IL-15, like IL-2, up-regulates expression of IL-2R alpha on human T and B cells, but rapidly down-regulates IL-15 high-affinity binding sites, which represent IL-15R alpha. This leads to a decreased responsiveness to IL-15 as measured by induction of Jak3 tyrosine phosphorylation. These results suggest a mechanism by which IL-15, a product of activated macrophages, may cooperate with IL-2 at the initiation of an immune response and enhance subsequent IL-2 responsiveness during T cell expansion.
Kumaki
S
S
Department of Molecular Biology, Immunex Research and Development Corporation, WA 98101, USA. Kumakis@immunex.com
Armitage
R
R
Ahdieh
M
M
Park
L
L
Cosman
D
D
D001402:B-Lymphocytes / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D019409:Interleukin-15; D007378:Interleukins / Q000502:physiology*; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D015854:Up-Regulation
C508024:IL15RA protein, human; D019409:Interleukin-15; D007378:Interleukins; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3