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.