Activation of naive and memory T cells by interleukin-15.
Interleukin-15 (IL-15), a product of monocytes and other cells, has biological activities similar to those of IL-2, including growth stimulation of activated T cells, induction of cytolytic effector cells, and B-cell costimulation for proliferation and lg production. We report that IL-15 at optimal concentrations rapidly induced memory (CD45RO+) CD4+ and CD8+ T cells and naive (CD45RO-) CD8+ T cells to express the CD69 activation marker followed by proliferation. By contrast, IL-15 failed to induce naive (CD45RO-) CD4+ T cells to express CD69 or to proliferate. Similar findings were obtained with IL-2. Unlike the other T-cell subsets, CD4+ T cells with a naive phenotype expressed little or no IL-2R beta chain, a shared component of the IL-2 and IL-15 receptors required for receptor function. A monoclonal antibody to the IL-2R beta chain, Mik beta 1, reduced CD69 expression and proliferation in CD4+ memory, CD8+ memory, and CD8+ naive T cells activated by IL-15. These results confirm the biological similarities of IL-2 and IL-15. They further document that the pool of naive CD4+ cells, unlike the pool of memory CD4+, memory CD8+, and naive CD8+ cells, is not regulated directly by the T-cell growth factors IL-2 or IL-15.
Kanegane
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Division of Hematologic Products, Food and Drug Administration, Bethesda, MD 20852, USA.
Tosato
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D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D019409:Interleukin-15; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019409:Interleukin-15; D007376:Interleukin-2; D007378:Interleukins; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C508024:IL15RA protein, human