Molecular, Cellular, and Functional Characterization of Chicken Cytokines Homologous to Mammalian IL-15 and IL-2

DNA sequence analysis of a chicken interleukin (IL)-15 cDNA identified a 187 amino acid open reading frame encoding a protein with a predicted molecular weight of 21,964Da, two potential N-linked glycosylation sites, four highly conserved Cys residues, two out-of-frame AUG initiation codons in the 5' untranslated region, and an unusually long (66 amino acid) signal peptide such that the expected size of the mature protein is 14,462Da. Chicken IL-15 and IL-2 were compared with regard to their molecular, cellular, and functional characteristics. The predicted amino acid sequences of both chicken cytokines showed greater homologies with mammalian IL-15s compared with mammalian IL-2s. Northern hybridization and RT-PCR demonstrated chicken IL-15 gene transcripts in a wide variety of tissues and cell types while the chicken IL-2 gene was expressed only in concanavalin A (con A)-activated spleen cells. Both recombinant cytokines stimulated the growth of spleen T-cells and enhanced the activity of natural killer (NK) cells in vitro. Subcutaneous injection with an expression plasmid encoding IL-15 increased the percentage of CD3+ spleen T-lymphocytes whereas injection of an IL-2 cDNA augmented CD3+, CD4+, CD8+, T-cell receptor (TCR)1+, and TCR2+ T-cells. Collectively, these results indicate that chicken IL-15 and IL-2 are T-cell growth factors potentially capable of enhancing cell-mediated immunity in vivo.