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Title: MOLECULAR, CELLULAR AND FUNCTIONAL CHARACTERIZATION OF CHICKEN CYTOKINES HOMOLOGOUS TO MAMMALIAN IL-15 AND IL-2

Author
item Lillehoj, Hyun
item MIN, WONGI - USDA, ARS, PBESL
item CHOI, KANGDUCK - USDA, ARS, IDRL
item BABU, UMA - FDA LAUREL MD
item BURNSIDE, JOAN - U DELAWARE, NEWARK
item MIYAMOTO, TADASHI - USDA, ARS, IDRL
item Rosenthal, Benjamin
item LILLEHOJ, ERIK - U MD BALTIMORE

Submitted to: Journal of Interferon and Cytokine Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2001
Publication Date: N/A
Citation: N/A

Interpretive Summary: Avian coccidiosis is caused by several different species of Eimeria parasites. Infection with coccidia causes intensive intestinal damage and poor nutrient absorption. Currently coccidiosis is managed by prophylactic medication. Ability to develop a novel coccidiosis vaccine will enhance poultry production world wide. However, the development of novel control strategy for coccidiosis is hampered by our lack of understanding of host immunity to coccidia. In this paper, ARS scientists identified a cytokine called interleukin-15(IL-15) which enhances host natural immunity against coccidia parasites. This factor is secreted by activated chicken lymphocytes and the gene which encodes this cytokine has been cloned. Recombinant cytokine was biologically active and promoted the growth of thymus-derived lymphocytes in chickens. Although limited information is available on the biological function of IL-15, studies in mammalian systems sindicate that it plays a pivotal role in the development, survival, and activity of natural killer (NK), mast, and muscle and may constitute an important component of cancer immunity, allograft rejection, and pathogenesis of autoimmune diseases where mononuclear cell infiltration is a hallmark feature. Treatment of chickens with this factor enhanced host immunity against coccidia. This finding indicate that naturally-derived lymphocyte factor can be used to increase coccidiosis disease resistance. This information will facilitate the development of novel immunological control strategy against avian diseases including coccidiosis.

Technical Abstract: DNA sequence analysis of a chicken IL-15 cDNA identified a 187 amino acid open reading frame encoding a protein with a predicted molecular weight of 21,964, 2 potential N-linked glycosylation sites, 4 highly conserved Cys residues, 2 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 14,462 Daltons. Chicken IL-15 and I were compared with regards to their molecular, cellular, and functional characteristics. The predicted amino acid sequences of both chicken cytokin 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 I 2 gene was expressed only in concanavalin A-activated spleen cells. Both recombinant cytokines stimulated the growth of spleen T cells and enhanced the activity of natural killer cells in vitro. Subcutaneous injection with expression plasmid encoding IL-15 increased the percentage of CD3+ spleen T lymphocytes whereas injection of an IL-2 cDNA augmented CD3+, CD4+, CD8+, TCR1+, 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.