IL-15 and IL-15Ralpha in CD4+T cell immunity.
The cytokine IL-15 performs numerous functions, such as promotion of growth and survival, on a plethora of cell types from both the lymphoid and non-lymphoid compartments. Therefore, mice genetically engineered to either lack or overexpress functional IL-15 display reduced immunological responses and leukemia, respectively. Surprisingly, IL-15 protein is hardly found in serum or body fluids. Due to the lack of a clear demonstration of its presence as protein,IL-15 was often referred to as a "ghost cytokine ". Recently, however, membrane-bound IL-15 was detected in both a membrane-anchored form and an IL-15Ralpha -bound form on monocytes. Interestingly, the latter complex can ben transpresented to cells expressing the intermediate-affinity IL-2/15Rbeta-gamma C receptor and thereby support the survival and proliferation of T cells. Moreover, overlapping promoter elements indicate a model of co-regulation of IL-15 and IL-15Ralpha by which IL-15 activities are controlled in a cell-contact-dependent manner. In this review, recent reports on IL-15 are combined with previous observations and discussed in terms of their functional consequences for CD4+ T cell responses.
Van Belle
Tom
T
Molecular Immunology Unit, Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB) and Laboratory for Molecular Biology, University of Ghent, Gent-Zwijnaarde, Belgium. tom.vanbelle@dmbr.urgent.be
Grooten
Johan
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2