마우스 비장세포의 증식과 생존율에 대한 BCG-CWS의 면역자극 효과 = Immunostimulatory effects of BCG-CWS on the proliferation and viability of mouse spleen cells

다국어 초록 (Multilingual Abstract)

Mycobacterial cell-wall skeleton (CWS) is an immunoactive and biodegradable particulate adjuvant and has been tried to use for immunotherapy. The CWS of Mycobacterium bovis bacillus Calmette-Guerin (BCG-CWS) was studied as an universal vaccine vehicle for antigen conjugation, to develop potentially effective and safe vaccine. Although a variety of biological activities of BCG-CWS have been studied, the effects of BCG-CWS on spleen cells are not fully elucidated. Using MTT assay and trypan blue exclusion test, we found that BCG-CWS significantly enhanced the viability and proliferation of cells. Multiple clusters, indicating proliferation, were observed in BCG-CWS-treated spleen cells and surface marker staining assay revealed that BCG-CWS promoted the proliferation of $CD19^+$ B lymphocyte rather than $CD4^+$ or $CD8^+$ T lymphocyte. In addition, BCG-CWS up-regulated the expression of anti-apoptotic molecules such as bcl-2, bcl-xL. BCG-CWS increased the surface expression of CD25 and CD69 as well as IL-2 production of spleen cells, suggesting increased activation. Furthermore, BCG-CWS enhanced the antigen-specific cell proliferation and interferon-gamma production of spleen cells. Taken together, these results demonstrate the immunostimulatory effects of BCG-CWS on spleen cells via multiple mechanisms, providing valuable information to broaden the use of BCG-CWS in clinical and research settings.

참고문헌 (Reference)

1 Brennan PJ, "The envelope of mycobacteria" 64 : 29-63, 1995

2 Fine PE, "The BCG story: lessons from the past and implications for the future" 11 (11): 353-359, 1989

3 Goto N, "Studies on the toxicities of aluminium hydroxide and calcium phosphate as immunological adjuvants for vaccines" 11 : 914-918, 1993

4 Uehori J, "Simultaneous blocking of human Toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Mycobacterium bovis bacillus Calmette-Guérin peptidoglycan" 71 : 4238-4249, 2003

5 Yun-Young Byon, "Radioprotective effects of fucoidan on bone marrow cells: improvement of the cell survival and immunoreactivity" 대한수의학회 9 (9): 359-365, 2008

6 Hong-Gu Joo, "Radioprotective effects of an acidic polysaccharide of Panaxginseng on bone marrow cells" 대한수의학회 8 (8): 39-44, 2007

7 Ochiai T, "Postoperative adjuvant immunotherapy of gastric cancer with BCG-cell wall skeleton. 3- to 6- year follow up of a randomized clinical trial" 14 : 167-171, 1983

8 Petrovsky N, "Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity" 24 (24): 2006

9 Mbow ML, "New adjuvants for human vaccines" 22 : 411-416, 2010

10 Begum NA, "Mycobacterium bovis BCG cell wall-specific differentially expressed genes identified by differential display and cDNA subtraction in human macrophages" 72 : 937-948, 2004

11 Mannhalter JW, "Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation" 61 : 143-151, 1985

12 Lambrecht BN, "Mechanism of action of clinically approved adjuvants" 21 : 23-29, 2009

13 Tsuji S, "Maturation of human dendritic cells by cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guérin: involvement of toll-like receptors" 68 : 6883-6890, 2000

14 Paul WE, "Lymphocyte responses and cytokines" 76 : 241-251, 1994

15 Goto N, "Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties" 15 : 1364-1371, 1997

16 Martín-Fontecha A, "Induced recruitment of NK cells to lymph nodes provides IFNgamma for T(H)1 priming" 5 : 1260-1265, 2004

17 Yamamura Y, "Immunotherapy of cancer with cell wall skeleton of Myocabacterium bovis-Bacillus Calmette-Guérin: experimental and clinical results" 277 : 209-227, 1976

18 Joo HG, "Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes" 69 : 555-564, 2001

19 Colditz GA, "Efficacy of BCG vaccine in the prevention of tuberculosis. Metaanalysis of the published literature" 271 : 698-702, 1994

20 Trunz BB, "Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness" 367 : 1173-1180, 2006

21 Brunelle JK, "Control of mitochondrial apoptosis by the Bcl-2 family" 122 : 437-441, 2009

22 Straw BE, "Comparison of tissue reactions produced by Haemophilus pleuropneumoniae vaccines made with six different adjuvants in swine" 49 : 149-151, 1985

23 Rhoades ER, "Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components" 85 : 159-176, 2005

24 Danial NN, "Cell death: critical control points" 116 : 205-219, 2004

25 Sancho D, "CD69 is an immunoregulatory molecule induced following activation" 26 : 136-140, 2005

26 Azuma I, "Biologically active components from mycobacterial cell walls. I. Isolation and composition of cell wall skeleton and component P3" 52 : 95-101, 1974

27 Rush JS, "B cells activated via CD40 and IL-4 undergo a division burst but require continued stimulation to maintain division, survival and differentiation" 31 : 1150-1159, 2001

28 Audibert FM, "Adjuvants: current status,clinical perspectives and future prospects" 14 : 281-284, 1993

29 Quigley M, "A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infection" 113 : 2256-2264, 2009