細胞素有免疫調節的功能，因此極具潛力開發為疫苗佐劑。基於此，我們評估以雞重組介白素2 (recombinant chicken interleukin-2, rChIL-2) 與雞重組介白素18 (recombinant chicken interleukin-18, rChIL-18) 做為傳染性華氏囊病 (infectious bursal disease, IBD) 疫苗佐劑的效力。IBD是由傳染性華氏囊病毒 (infectious bursal disease virus, IBDV) 感染所引起的高度傳染性疾病，此病會造成雛雞免疫抑制，因此對於全世界的畜產業有相大的威脅。為了探討施打rChIL-2、rChIL-18、rChIL-2 與 rChIL-18，對於IBD疫苗免疫後的差異，我們檢測比較各組雞隻在施打疫苗後的免疫反應。依據抗體反應、細胞素表現情形、組織學分析來評估各細胞素佐劑效力。實驗結果顯示，疫苗免疫時同時給予rChIL-2 (1 micro-g)或rChIL-2/rChIL-18 (0.1/1 micro-g)細胞素，可增強雞隻體液性免疫反應，提升IL-2受體alpha鏈 (CD25)、丙型干擾素 (interferon-gamma，IFN-gamma)、誘導型一氧化氮合成酶 (inducible nitric oxide synthase，iNOS) 的基因表現，並減輕雞隻在受IBDV攻擊後華氏囊受損的情形。總結以上研究，使用雞重組介白素2及雞重組介白素18皆可增強傳染性IBD疫苗的免疫原性，可視為好的疫苗佐劑。

Cytokines have been considered as potential candidates for vaccine adjuvants based on their immunoregulatory roles. In this study, we evaluated the efficacy of recombinant chicken interleukin-2 (rChIL-2) and recombinant chicken interleukin-18 (rChIL-18) as vaccine adjuvants to combat against the infectious bursal disease virus (IBDV). Infectious bursal disease (IBD) is an acute contagious viral disease caused by infections of IBDV, resulting in severe immunosupression in young chickens, and therefore threatens to the poultry worldwide. After immunization of IBD vaccine with or without coadministration of rChIL-2, rChIL-18, and rChIL-2 plus rChIL-18, we examined and compared immune responses among vaccinated chickens. The adjuvancity of cytokines was assessed based on antibody responses, cytokine expressions, and histological analyses. Vaccination with rChIL-2 (1 micro-g) or rChIL-2/rChIL-18 (0.1/1 micro-g) significantly enhanced humoral immune response, upregulated gene expression of CD25, IFN-gamma, and inducible nitric oxide synthase (iNOS), and reduced lesions of bursa after IBDV challenge. In conclusion, both rChIL-2 and rChIL-18 may serve as good adjuvants to enhance the immunogenicity of IBD vaccine.

目次------------------------------------------------------------------------ I
中文摘要-------------------------------------------------------------------III
英文摘要-------------------------------------------------------------------IV
圖表索引-------------------------------------------------------------------V
中英文對照表-------------------------------------------------------------VII
第一章　序言-------------------------------------------------------------1
第二章　文獻探討-------------------------------------------------------3
第一節 傳染性華氏囊病 (infectious bursal disease, IBD)-3
1-1 IBD簡介------------------------------------------------- 3
1-2 IBD病史--------------------------------------------------3
1-3 IBDV特性------------------------------------------------4
1-4 IBDV抗原性與致病性---------------------------------5
1-5 IBD病徵與防疫-----------------------------------------5
第二節 細胞素 (cytokine)----------------------------------------7
2-1 細胞素簡介-----------------------------------------------7
2-2 介白素2 (interleukin-2, IL-2)--------------------------7
2-2-1 IL-2的發現-----------------------------------------7
2-2-2 IL-2生物特性--------------------------------------8
2-2-3 IL-2目前的應用-----------------------------------10
2-3 雞介白素2 (chicken IL-2, ChIL-2) 簡介------------10
2-3-1 ChIL-2的發現-------------------------------------10
2-3-2 ChIL-2生物特性----------------------------------11
2-4 介白素18 (interleukin-18, IL-18) 簡介--------------11
2-4 IL-18的發現----------------------------------------------12
2-4-2 IL-18生物特性-------------------------------------12
2-4-3 IL-18的應用----------------------------------------14
2-5 雞介白素18 (chicken IL-18, ChIL-18)----------------15
2-5-2 ChIL-18的發現與生物特性----------------------15
第三節 疫苗佐劑開發----------------------------------------------15
第三章　材料與方法-------------------------------------------------------19
第四章　結果-----------------------------------------------------------------30
4-1 重組蛋白純化----------------------------------------------------30
4-1-1 rChIL-2純化----------------------------------------------30
4-1-3 rChIL-18純化---------------------------------------------30
4-2 細胞素安全劑量測試與有效劑量評估-----------------------31
4-3 rChIL-2、rChIL-18做為傳染性華氏囊病疫苗佐劑效力評估 I 32
4-3-1 偵測CD25、IFN-gamma基因表現與血清中抗體力價--------- 32
4-3-2 華氏囊組織病理評估-------------------------------------34
4-3-3 臨床徵狀----------------------------------------------------35
4-3-4 綜觀細胞素疫苗佐劑效力------------------------------- 35
4-4 rChIL-2、rChIL-18 做為傳染性華氏囊病疫苗佐劑效力評估II 37
4-4-1 Th1 相關基因表現----------------------------------------- 37
4-4-2 檢測血清中IBDV抗體力價----------------------------- 38
4-4-3 檢測血清中ND抗體力價-------------------------------- 40
4-4-4 華氏囊組織病理分析-------------------------------------- 41
第五章　討論-------------------------------------------------------------------- 44
圖表-------------------------------------------------------------------------------- 52
參考文獻-------------------------------------------------------------------------- 78

Ahlers, J.D., Belyakov, I.M., Matsui, S., and Berzofsky, J.A. (2001). Mechanisms of cytokine synergy essential for vaccine protection against viral challenge. Int Immunol 13, 897-908.
Ahlers, J.D., Dunlop, N., Alling, D.W., Nara, P.L., and Berzofsky, J.A. (1997). Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. J Immunol 158, 3947-3958.
Beadling, C., Guschin, D., Witthuhn, B.A., Ziemiecki, A., Ihle, J.N., Kerr, I.M., and Cantrell, D.A. (1994). Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, but not the T cell antigen receptor, in human T lymphocytes. The EMBO journal 13, 5605-5615.
Blackman, M.A., Tigges, M.A., Minie, M.E., and Koshland, M.E. (1986). A model system for peptide hormone action in differentiation: interleukin 2 induces a B lymphoma to transcribe the J chain gene. Cell 47, 609-617.
Brandt, M., Yao, K., Liu, M., Heckert, R.A., and Vakharia, V.N. (2001). Molecular determinants of virulence, cell tropism, and pathogenic phenotype of infectious bursal disease virus. J Virol 75, 11974-11982.
Brennan, P., Babbage, J.W., Burgering, B.M., Groner, B., Reif, K., and Cantrell, D.A. (1997). Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity 7, 679-689.
Burbach, G.J., Naik, S.M., Harten, J.B., Liu, L., Dithmar, S., Grossniklaus, H., Ward, S.L., Armstrong, C.A., Caughman, S.W., and Ansel, J.C. (2001). Interleukin-18 expression and modulation in human corneal epithelial cells. Curr Eye Res 23, 64-68.
Charlton, B.R., Bermudez, A.J., Boulianne, M., Halvorson, D.A., Schrader, J.S., Newman, L.J., Sander, J.E., and Wakenell, P.S. (1957). Avian Disease Manual American Association of Avian Pathologists [etc].
Degen, W.G., van Zuilekom, H.I., Scholtes, N.C., van Daal, N., and Schijns, V.E. (2005). Potentiation of humoral immune responses to vaccine antigens by recombinant chicken IL-18 (rChIL-18). Vaccine 23, 4212-4218.
Dillman, R.O. (1994). The clinical experience with interleukin-2 in cancer therapy. Cancer Biother 9, 183-209.
Dobos, P., Hill, B.J., Hallett, R., Kells, D.T., Becht, H., and Teninges, D. (1979). Biophysical and biochemical characterization of five animal viruses with bisegmented double-stranded RNA genomes. J Virol 32, 593-605.
Dunham, S.P., Flynn, J.N., Rigby, M.A., Macdonald, J., Bruce, J., Cannon, C., Golder, M.C., Hanlon, L., Harbour, D.A., Mackay, N.A., et al. (2002). Protection against feline immunodeficiency virus using replication defective proviral DNA vaccines with feline interleukin-12 and -18. Vaccine 20, 1483-1496.
Eberl, M., Beck, E., Coulson, P.S., Okamura, H., Wilson, R.A., and Mountford, A.P. (2000). IL-18 potentiates the adjuvant properties of IL-12 in the induction of a strong Th1 type immune response against a recombinant antigen. Vaccine 18, 2002-2008.
Fujioka, N., Akazawa, R., Ohashi, K., Fujii, M., Ikeda, M., and Kurimoto, M. (1999). Interleukin-18 protects mice against acute herpes simplex virus type 1 infection. J Virol 73, 2401-2409.
Gaffen, S.L., and Liu, K.D. (2004). Overview of interleukin-2 function, production and clinical applications. Cytokine 28, 109-123.
Gaffen, S.L., Wang, S., and Koshland, M.E. (1996). Expression of the immunoglobulin J chain in a murine B lymphoma is driven by autocrine production of interleukin 2. Cytokine 8, 513-524.
Gardella, S., Andrei, C., Costigliolo, S., Poggi, A., Zocchi, M.R., and Rubartelli, A. (1999). Interleukin-18 synthesis and secretion by dendritic cells are modulated by interaction with antigen-specific T cells. J Leukoc Biol 66, 237-241.
Ghayur, T., Banerjee, S., Hugunin, M., Butler, D., Herzog, L., Carter, A., Quintal, L., Sekut, L., Talanian, R., Paskind, M., et al. (1997). Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386, 619-623.
Giedraitis, V., He, B., Huang, W.X., and Hillert, J. (2001). Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. Journal of neuroimmunology 112, 146-152.
Glenny AT, P.C., Waddington H, and Wallace U. (1926). The antigenic value of toxoid precipitated by potassium alum. J Pathol Bacteriol 29, 38-39.
Gobel, T.W., Schneider, K., Schaerer, B., Mejri, I., Puehler, F., Weigend, S., Staeheli, P., and Kaspers, B. (2003). IL-18 stimulates the proliferation and IFN-gamma release of CD4+ T cells in the chicken: conservation of a Th1-like system in a nonmammalian species. J Immunol 171, 1809-1815.
Good, M.F., Pombo, D., Lunde, M.N., Maloy, W.L., Halenbeck, R., Koths, K., Miller, L.H., and Berzofsky, J.A. (1988). Recombinant human IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides. Correlation of effect with biologic activity of IL-2. J Immunol 141, 972-977.
Gu, Y., Kuida, K., Tsutsui, H., Ku, G., Hsiao, K., Fleming, M.A., Hayashi, N., Higashino, K., Okamura, H., Nakanishi, K., et al. (1997). Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science 275, 206-209.
Hsieh, M.K., Wu, C.C., and Lin, T.L. (2006). The effect of co-administration of DNA carrying chicken interferon-gamma gene on protection of chickens against infectious bursal disease by DNA-mediated vaccination. Vaccine 24, 6955-6965.
Hsieh, M.K., Wu, C.C., and Lin, T.L. (2007). Priming with DNA vaccine and boosting with killed vaccine conferring protection of chickens against infectious bursal disease. Vaccine 25, 5417-5427.
Hughes-Fulford, M., Sugano, E., Schopper, T., Li, C.F., Boonyaratanakornkit, J.B., and Cogoli, A. (2005). Early immune response and regulation of IL-2 receptor subunits. Cellular Signalling 17, 1111-1124.
Hulse, D.J., and Romero, C.H. (2004). Partial protection against infectious bursal disease virus through DNA-mediated vaccination with the VP2 capsid protein and chicken IL-2 genes. Vaccine 22, 1249-1259.
Jackwood, D.J., Saif, Y.M., and Hughes, J.H. (1982). Characteristics and serologic studies of two serotypes of infectious bursal disease virus in turkeys. Avian Dis 26, 871-882.
Kaiser, P., and Mariani, P. (1999). Promoter sequence, exon:intron structure, and synteny of genetic location show that a chicken cytokine with T-cell proliferative activity is IL2 and not IL15. Immunogenetics 49, 26-35.
Kato, Z., Jee, J., Shikano, H., Mishima, M., Ohki, I., Ohnishi, H., Li, A., Hashimoto, K., Matsukuma, E., Omoya, K., et al. (2003). The structure and binding mode of interleukin-18. Nature structural biology 10, 966-971.
Kaufer, I., and Weiss, E. (1980). Significance of bursa of Fabricius as target organ in infectious bursal disease of chickens. Infection and immunity 27, 364-367.
Kawamura, H., Rosenberg, S.A., and Berzofsky, J.A. (1985). Immunization with antigen and interleukin 2 in vivo overcomes Ir gene low responsiveness. J Exp Med 162, 381-386.
Khatri, M., Palmquist, J.M., Cha, R.M., and Sharma, J.M. (2005). Infection and activation of bursal macrophages by virulent infectious bursal disease virus. Virus Res 113, 44-50.
Kibenge, F.S., Dhillon, A.S., and Russell, R.G. (1988). Biochemistry and immunology of infectious bursal disease virus. J Gen Virol 69 ( Pt 8), 1757-1775.
Kim, I.J., Karaca, K., Pertile, T.L., Erickson, S.A., and Sharma, J.M. (1998). Enhanced expression of cytokine genes in spleen macrophages during acute infection with infectious bursal disease virus in chickens. Vet Immunol Immunopathol 61, 331-341.
Kohno, K., and Kurimoto, M. (1998). Interleukin 18, a cytokine which resembles IL-1 structurally and IL-12 functionally but exerts its effect independently of both. Clin Immunol Immunopathol 86, 11-15.
Lewis, P.J., and Babiuk, L.A. (1999). DNA vaccines: a review. Advances in virus research 54, 129-188.
Lillehoj, H.S., Min, W., Choi, K.D., Babu, U.S., Burnside, J., Miyamoto, T., Rosenthal, B.M., and Lillehoj, E.P. (2001). Molecular, cellular, and functional characterization of chicken cytokines homologous to mammalian IL-15 and IL-2. Vet Immunol Immunopathol 82, 229-244.
Liu, Y., Huang, H., Saxena, A., and Xiang, J. (2002). Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumors. Cancer Gene Ther 9, 533-542.
Lofthouse, S.A., Andrews, A.E., Elhay, M.J., Bowles, V.M., Meeusen, E.N., and Nash, A.D. (1996). Cytokines as adjuvants for ruminant vaccines. Int J Parasitol 26, 835-842.
Lori, F., Weiner, D.B., Calarota, S.A., Kelly, L.M., and Lisziewicz, J. (2006). Cytokine-adjuvanted HIV-DNA vaccination strategies. Springer Seminars In Immunopathology 28, 231-238.
Lowenthal, J.W., Zubler, R.H., Nabholz, M., and MacDonald, H.R. (1985). Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature 315, 669-672.
Lu, Y.L., and Shieh, H.K. (1983). Infectious bursal disease in Taiwan. . Journal of the Chinese Society of Veterinary Science 9, 61-66.
Mahmood, M.S., Siddique, M., Hussain, I., Khan, A., and Mansoor, M.K. (2006). Protection capability of recombinant plasmid DNA vaccine containing VP2 gene of very virulent infectious bursal disease virus in chickens adjuvanted with CpG oligodeoxynucleotide. Vaccine 24, 4838-4846.
Matsumoto, S., Tsuji-Takayama, K., Aizawa, Y., Koide, K., Takeuchi, M., Ohta, T., and Kurimoto, M. (1997). Interleukin-18 activates NF-kappaB in murine T helper type 1 cells. Biochem Biophys Res Commun 234, 454-457.
Morgan, D.A., Ruscetti, F.W., and Gallo, R. (1976). Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193, 1007-1008.
Muller, H., Islam, M.R., and Raue, R. (2003). Research on infectious bursal disease--the past, the present and the future. Veterinary microbiology 97, 153-165.
Mundt, E., Kollner, B., and Kretzschmar, D. (1997). VP5 of infectious bursal disease virus is not essential for viral replication in cell culture. Journal Of Virology 71, 5647-5651.
Nakamura, K., Okamura, H., Wada, M., Nagata, K., and Tamura, T. (1989). Endotoxin-induced serum factor that stimulates gamma interferon production. Infect Immun 57, 590-595.
Nakanishi, K., Yoshimoto, T., Tsutsui, H., and Okamura, H. (2001). Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19, 423-474.
Nick, H., Cursiefen, D., and Becht, H. (1976). Structural and growth characteristics of infectious bursal disease virus. J Virol 18, 227-234.
Novick, D., Kim, S.H., Fantuzzi, G., Reznikov, L.L., Dinarello, C.A., and Rubinstein, M. (1999). Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response. Immunity 10, 127-136.
O''Hagan, D.T., MacKichan, M.L., and Singh, M. (2001). Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng 18, 69-85.
Okamura, H., Tsutsi, H., Komatsu, T., Yutsudo, M., Hakura, A., Tanimoto, T., Torigoe, K., Okura, T., Nukada, Y., Hattori, K., et al. (1995). Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378, 88-91.
Olencki, T., Malhi, S., Mekhail, T., Dreicer, R., Elson, P., Wood, L., and Bukowski, R.M. (2006). Phase I trial of thalidomide and interleukin-2 in patients with metastatic renal cell carcinoma. Invest New Drugs 24, 321-326.
Palmquist, J.M., Khatri, M., Cha, R.M., Goddeeris, B.M., Walcheck, B., and Sharma, J.M. (2006). In vivo activation of chicken macrophages by infectious bursal disease virus. In Viral Immunol, pp. 305-315.
Perkins, G.R., Marvel, J., and Collins, M.K. (1993). Interleukin 2 activates extracellular signal-regulated protein kinase 2. J Exp Med 178, 1429-1434.
Pirhonen, J. (2001). Regulation of IL-18 expression in virus infection. Scand J Immunol 53, 533-539.
Rautenschlein, S., Kraemer, C., Vanmarcke, J., and Montiel, E. (2005). Protective efficacy of intermediate and intermediate plus infectious bursal disease virus (IBDV) vaccines against very virulent IBDV in commercial broilers. Avian Dis 49, 231-237.
Rautenschlein, S., Yeh, H.Y., Njenga, M.K., and Sharma, J.M. (2002). Role of intrabursal T cells in infectious bursal disease virus (IBDV) infection: T cells promote viral clearance but delay follicular recovery. Arch Virol 147, 285-304.
Refaeli, Y., Van Parijs, L., London, C.A., Tschopp, J., and Abbas, A.K. (1998). Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis. Immunity 8, 615-623.
Reznikov, L.L., Kim, S.H., Westcott, J.Y., Frishman, J., Fantuzzi, G., Novick, D., Rubinstein, M., and Dinarello, C.A. (2000). IL-18 binding protein increases spontaneous and IL-1-induced prostaglandin production via inhibition of IFN-gamma. Proc Natl Acad Sci U S A 97, 2174-2179.
Riddell, C. (1996). Avian Histopathology
Schneider, K., Puehler, F., Baeuerle, D., Elvers, S., Staeheli, P., Kaspers, B., and Weining, K.C. (2000). cDNA cloning of biologically active chicken interleukin-18. J Interferon Cytokine Res 20, 879-883.
Schnetzler, M., Oommen, A., Nowak, J.S., and Franklin, R.M. (1983). Characterization of chicken T cell growth factor. Eur J Immunol 13, 560-566.
Sharma, J.M., Kim, I.J., Rautenschlein, S., and Yeh, H.Y. (2000). Infectious bursal disease virus of chickens: pathogenesis and immunosuppression. Dev Comp Immunol 24, 223-235.
Shi, X.J., Wang, B., and Wang, M. (2007). Immune enhancing effects of recombinant bovine IL-18 on foot-and-mouth disease vaccination in mice model. Vaccine 25, 1257-1264.
Stepaniak, J.A., Shuster, J.E., Hu, W., and Sundick, R.S. (1999). Production and in vitro characterization of recombinant chicken interleukin-2. J Interferon Cytokine Res 19, 515-526.
Sundick, R.S., and Gill-Dixon, C. (1997). A cloned chicken lymphokine homologous to both mammalian IL-2 and IL-15. J Immunol 159, 720-725.
Tacken, M.G., Rottier, P.J., Gielkens, A.L., and Peeters, B.P. (2000). Interactions in vivo between the proteins of infectious bursal disease virus: capsid protein VP3 interacts with the RNA-dependent RNA polymerase, VP1. J Gen Virol 81, 209-218.
Tanaka-Kataoka, M., Kunikata, T., Takayama, S., Iwaki, K., Ohashi, K., Ikeda, M., and Kurimoto, M. (1999). In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection. Cytokine 11, 593-599.
Thomson, A.W.L., Michael T. (2003). The cytokine handbook. Amsterdam ;Academic Press.
Thornton, S., Kuhn, K.A., Finkelman, F.D., and Hirsch, R. (2001). NK cells secrete high levels of IFN-gamma in response to in vivo administration of IL-2. Eur J Immunol 31, 3355-3360.
Tone, M., Thompson, S.A., Tone, Y., Fairchild, P.J., and Waldmann, H. (1997). Regulation of IL-18 (IFN-gamma-inducing factor) gene expression. J Immunol 159, 6156-6163.
Tovey, M.G., Meritet, J.F., Guymarho, J., and Maury, C. (1999). Mucosal cytokine therapy: marked antiviral and antitumor activity. J Interferon Cytokine Res 19, 911-921.
Tsukamoto, K., Tanimura, N., Kakita, S., Ota, K., Mase, M., Imai, K., and Hihara, H. (1995). Efficacy of three live vaccines against highly virulent infectious bursal disease virus in chickens with or without maternal antibodies. Avian Dis 39, 218-229.
van den Berg, T.P., Eterradossi, N., Toquin, D., and Meulemans, G. (2000). Infectious bursal disease (Gumboro disease). Revue scientifique et technique (International Office of Epizootics) 19, 509-543.
Waldmann, T.A., Dubois, S., and Tagaya, Y. (2001). Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14, 105-110.
Watson, J., Gillis, S., Marbrook, J., Mochizuki, D., and Smith, K.A. (1979). Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. J Exp Med 150, 849-861.
Xin, K.Q., Hamajima, K., Sasaki, S., Tsuji, T., Watabe, S., Okada, E., and Okuda, K. (1999). IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine. Vaccine 17, 858-866.
Yao, K., Goodwin, M.A., and Vakharia, V.N. (1998). Generation of a mutant infectious bursal disease virus that does not cause bursal lesions. J Virol 72, 2647-2654.
Yeh, H.Y., Rautenschlein, S., and Sharma, J.M. (2002). Protective immunity against infectious bursal disease virus in chickens in the absence of virus-specific antibodies. Vet Immunol Immunopathol 89, 149-158.
Zhang, X., Sun, S., Hwang, I., Tough, D.F., and Sprent, J. (1998). Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8, 591-599.
Zubler, R.H., Lowenthal, J.W., Erard, F., Hashimoto, N., Devos, R., and MacDonald, H.R. (1984). Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med 160, 1170-1183.
黃瓊賢 (2002). 雞介白素-8 及雞介白素-18 cDNA 之選殖與重組蛋白表現. 碩士論文。中興大學獸醫微生物學研究所。臺灣省臺中市。中華民國。.
蔡淑婷 (2003). 雞介白素-2 之重組蛋白表現與應用。. 碩士論文。中興大學獸醫微生物學研究所。臺灣省臺中市。中華民國。.