Genes for each of the three related cytokines interleukin 2 (IL-2), IL-15 and IL-15-like (IL-15L) are present in fish and mammals, although intact IL-15L is lost in some species including human and mouse. The sequence conservation of binding motifs was corroborated by experiments showing interaction between the cytokines IL-2, IL-15 or IL-15L and the receptor IL-15Rα molecules of a fish, rainbow trout, and a mammal, cattle; only bovine IL-2 did not participate in these trout-cattle cross-interactions, as apparently IL-2 of tetrapod species has specialized towards binding the evolutionarily newer type receptor chain IL-2Rα. Stable secretion by transfected cells of IL-15 and IL-15L of both trout and cattle was found to be at least partially dependent on the co-expression with soluble IL-15Rα, whereas bovine and trout IL-2 expression showed little or no dependency on the co-expression with IL-15Rα or IL-2Rα. Distinct sensitivities of various trout lymphocyte populations as measured by STAT5 phosphorylation were found after stimulation by IL-2, IL-15 and IL-15L. Like in mammals, trout CD8+ lymphocytes were particularly sensitive to IL-15. The present study is the first report on an IL-15L function. The emerging picture is that, in part by means of different dependencies on interaction with IL-15Rα (or IL-2Rα), from the level of fish already jawed vertebrates employed the IL-2/15/15L family cytokines to distinguish between cell types in a more or less locally restricted manner.