Mapping quantitative trait loci for T lymphocyte subpopulations in peripheral blood in swine

BMC Genetics

Qin Zhang²  Yang Liu²  Zhi-Peng Wang²  Yuan-Fang Gong³  Jian-Feng Liu²  Xin Lu¹ 

[1] State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing 102206, China;Key Laboratory of Animal Genetics Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;Department of Animal Science, Hebei Normal University of Science and Technology, Changli, Hebei 066600, China

关键词: swine;    quantitative trait loci;    T lymphocyte subpopulations;   

Others  :  1122609
DOI  :  10.1186/1471-2156-12-79

 received in 2011-03-31, accepted in 2011-09-16,  发布年份 2011

【 摘 要 】

Background

Increased disease resistance through improved general immune capacity would be beneficial for the welfare and productivity of farm animals. T lymphocyte subpopulations in peripheral blood play an important role in immune capacity and disease resistance in animals. However, very little research to date has focused on quantitative trait loci (QTL) for T lymphocyte subpopulations in peripheral blood in swine.

Results

In the study, experimental animals consist of 446 piglets from three different breed populations. To identify QTL for T lymphocyte subpopulations in peripheral blood in swine, the proportions of CD4+, CD8+, CD4+CD8+, CD4+CD8-, CD4-CD8+, and CD4-CD8- T cells and the ratio of CD4+:CD8+ T cells were measured for all individuals before and after challenge with modified live CSF (classical swine fever) vaccine. Based on the combined data of individuals from three breed populations, genome-wide scanning of QTL for these traits was performed based on a variance component model, and the genome wide significance level for declaring QTL was determined via permutation tests as well as FDR (false discovery rate) correction. A total of 27 QTL (two for CD4+CD8+, one for CD4+CD8-, three for CD4-CD8+, two for CD4-CD8-, nine for CD4+, two for CD8+, and eight for CD4+:CD8+ ratio) were identified with significance level of FDR < 0.10, of which 11 were significant at the level of FDR < 0.05, including the five significant at FDR < 0.01.

Conclusions

Within these QTL regions, a number of known genes having potential relationships with the studied traits may serve as candidate genes for these traits. Our findings herein are helpful for identification of the causal genes underlying these immune-related trait and selection for immune capacity of individuals in swine breeding in the future.

【 授权许可】

   
2011 Lu et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Wiseman J, Varley MA, Chadwick JP: Progress in Pig Science. Nottingham: Nottingham University Press; 1998:29-38.
• [2]Visscher AH, Janss LLG, Niewold TA, De Greef KH: Disease incidence and immunological traits for the selection of healthy pigs. Vet Q 2002, 24:29-34.
• [3]Sinkora M, Butler JE, Holtmeier W, Sinkorova J: Lymphocyte development in fetal piglets: facts and surprises. Vet Immunol Immunopathol 2005, 108(1-2):177-184.
• [4]Alving K: Airways vasodilatation in the immediate allergic reaction. Involvement of inflammatory mediators and sensory nerves. Acta Physiol Scand Suppl 1991, 597:1-64.
• [5]Kenmochi T, Mullen Y, Miyamoto M, Stein E: Swine as an allotransplantation model. Veterinary Immunology and Immunopathology 1994, 43(1-3):177-1831.
• [6]Misfeldt ML, Grimm DR: Sinclair miniature swine: an animal model of human melanoma. Vet Immunol Immunopathol 1994, 43:161.
• [7]Reinherz EL, Schlossman SF: The differentiation and function of human T lymphocytes. Cell 1980, 19(4):821-827.
• [8]Doyle C, Strominger JL: Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 1987, 330(6145):256-259.
• [9]Buttini M, Westland CE, Masliah E, Yafeh AM, Wyss-Coray T, Mucke L: Novel role of human CD4 molecule identified in neurodegeneration. Nature Med 1998, 4:441-446.
• [10]Shedlock DJ, Shen H: Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 2003, 300:337-339.
• [11]Swain SL, Dutton RW, Schwab R, Yamamoto J: Xenogeneic human anti-mouse T cell responses are due to the activity of the same functional T cell subsets responsible for allospecific and major histocompatibilityrestricted responses. The Journal of Experimental Medicine 1983, 157:720.
• [12]Weiss A: T lymphocyte activation. Fundamental immunology 1997, 467-504.
• [13]Unanue ER: Macrophages, antigen-presenting cells, and the phenomena of antigen handling and presentation. Fundamental immunology 1993, 111-144.
• [14]Doherty PC, Topham DJ, Tripp RA: Establishment and persistance of virus-specific CD4+and CD8+T cell memory. Immunol Rev 1996, 150:23-44.
• [15]Ober BT, Summerfield A, Mattlinger C, Wiesmuller KH, Jung G, Pfaff E, Saalmuller A, Rziha HJ: Vaccine-induced, pseudorabies virus-specific, extrathymic CD4+CD8+ memory T-helper cells in swine. J Virol 1998, 72(6):4866-4873.
• [16]Yang XG, Zhang XY, Wang X: Effect of Chinese herbal medicine mixture on immune function in chickens. J Northeast Agric Univ 2005, 36:60-65.
• [17]Hu YJ, Lin YC, Zhou GL, Yu DQ: Effect of Chinese extracts on performance and T lymphocyte cell subset of yellow broilers. China Poult 2003, 12:14-17.
• [18]Damoiseaux JG, Cautain B, Bernard I, Mas M, Van Breda Vriesman PJ, Druet P, Fournie G, Saoudi A: A dominant role for the thymus and MHC genes in determining the peripheral CD4/CD8 T cell ratio in the rat. J Immunology 1999, 163:2983.
• [19]Salazar RA, Souza VL, Khan AS, Fleischman JK: Role of CD4:CD8 ratio in predicting HIV co-infection in patients with newly diagnosed tuberculosis. AIDS Patient Care STDS 2000, 14(2):79-83.
• [20]Binns RM, Duncan IA, Powis SJ, Hutchings A, Butcher G: Subsets of null and gamma delta T-cell receptor 1 T lymphocytes in the blood of young pigs identified by specific monoclonal antibodies. Immunology 1992, 177:219-227.
• [21]Carr MM, Howard CJ, Sopp P, Manser JM, Parsons KR: Expression of porcine g/d T lymphocytes of a phylogenetically conserved surface antigen previously restricted in expression of ruminant gd T lymphocytes. Immunology 1994, 81:36-40.
• [22]Hirt W, Saalmüller A, Reddehase JM: Distinct g/d T cell receptors define two subsets of circulating porcine CD22CD42CD82 Tlymphocytes. J Immunology 1990, 20:265-269.
• [23]Saalmüller A, Hirt W, Reddehase MJ: Porcine g/d T lymphocyte subsets differing in their propensity to home to the lymphoid tissue. Eur J Immunol 1990, 20:2343-2346.
• [24]Sinkora J, Rehakova Z, Sinkora M, Cukrowska B, Tlaskalova-Hogenova H: Early development of immune system in pigs. Vet Immunol Immunopathol 2002, 87(3-4):301-306.
• [25]Summerfield A, Rziha HJ, Saalmüller A: Functional characterization of porcine CD4+CD8+ extrathymic T lymphocytes. Cell Immunol 1996, 168:291-296.
• [26]Andersson L, Haley CS, Ellegren H, Knott SA, Johansson M, Andersson K, Andersson-Eklund L, Edfors-Lilja I, Fredholm M, Hansson I, et al.: Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 1994, 263:1771-1774.
• [27]Wattrang E, Almqvist M, Johansson A, Fossum C, Wallgren P, Pielberg G, Andersson L, Edfors-Lilja I: Confirmation of QTL on porcine chromosomes 1 and 8 influencing leukocyte numbers, haematological parameters and leukocyte function. Anim Genet 2005, 36(4):337-345.
• [28]Gong YF, Lu X, Wang ZP, Hu F, Luo YR, Cai SQ, Qi CM, Li S, Niu XY, Qiu XT, et al.: Detection of quantitative trait loci affecting haematological traits in swine via genome scanning. BMC Genet 2010, 11:56.
• [29]Edfors-Lilja I, Wattrang E, Marklund L, Moller M, Andersson-Eklund L, Andersson L, Fossum C: Mapping quantitative trait loci for immune capacity in the pig. J Immunology 1998, 160:829-835.
• [30]Edfors-Lilja I, Wattrang E, Andersson L, Fossum C: Mapping quantitative trait loci for stress induced alterations in porcine leukocyte numbers and functions. Animal Genetics 2000, 31:186-193.
• [31]Zou Z, Ren J, Yan X, Huang X, Yang S, Zhang Z, Yang B, Li W, Huang L: Quantitative trait loci for porcine baseline erythroid traits at three growth ages in a White Duroc 3 Erhualian F2 resource population. Mamm Genome 2008.
• [32]Reiner G, Fischer R, Hepp S, Berge T, Köhler F, Willems H: Quantitative trait loci for red blood cell traits in swine. Animal Genetics 2007, 38:447-452.
• [33]Reiner G, Fischer R, Hepp S, Berge T, Kohler F, Willems H: Quantitative trait loci for white blood cell numbers in swine. Anim Genet 2008, 39(2):163-168.
• [34]Lu X, Gong YF, Liu JF, Wang ZP, Hu F, Qiu XT, Luo YR, Zhang Q: Mapping quantitative trait loci for cytokines in the pig. Anim Genet 2011, 42(1):1-5.
• [35]Wilkie B, Mallard B: Selection for high immune response: an alternative approach to animal health maintenance. Vet Immunol Immunopathol 1999, 72:231-235.
• [36]Amadori A, Zamarchi R, Chieco-Bianchi L: CD4: CD8 ratio and HIV infection: the "tap-and-drain" hypothesis. Immunol Today 1996, 17:414-417.
• [37]Evans DM, Frazer IH, Martin NG: Genetic and environmental causes of variation in basal levels of blood cells. Twin Res 1999, 2:250-257.
• [38]Hall MA, Ahmadi KA, Norman P, Snieder H, Macgregor A, Vaughan RW, Spector TD, Lanchbury JS: Genetic influence on peripheral blood T lymphocyte levels. Genes Immun 2000, 1:423-427.
• [39]Ahmadi KR, Hall MA, Norman P, Vaughan RW, Snieder H, Spector TD, Lanchbury JS: Genetic determinism in the relationship between human CD4+ and CD8+ T lymphocyte populations? Genes Immun 2001, 2(7):381-387.
• [40]Liu Y, Luo YR, Lu X, Qiu XT, Fu WX, Zhou JP, Liu XY, Zhang Q, Yin ZJ: Investigation and Comparative Study on Haematological Traits, Lysozyme Concentration and T Lymphocyte Subpopulation in Three Pig Breeds. Journal of Animal and Veterinary Advances 2010, 9(21):2748-2751.
• [41]Kim JJ, Rothschild MF, Beever J, Rodriguez-Zas S, Dekkers JC: Joint analysis of two breed cross populations in pigs to improve detection and characterization of quantitative trait loci. J Anim Sci 2005, 83(6):1229-1240.
• [42]Perez-Enciso M, Mercade A, Bidanel JP, Geldermann H, Cepica S, Bartenschlager H, Varona L, Milan D, Folch JM: Large-scale, multibreed, multitrait analyses of quantitative trait loci experiments: the case of porcine × chromosome. J Anim Sci 2005, 83(10):2289-2296.
• [43]Walling GA, Visscher PM, Andersson L, Rothschild MF, Wang L, Moser G, Groenen MA, Bidanel JP, Cepica S, Archibald AL, et al.: Combined analyses of data from quantitative trait loci mapping studies. Chromosome 4 effects on porcine growth and fatness. Genetics 2000, 155(3):1369-1378.
• [44]Song XT, Evel-Kabler K, Shen L, Rollins L, Huang XF, Chen SY: A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression. Nat Med 2008, 14(3):258-265.
• [45]Tewari K, Sacha J, Gao X, Suresh M: Effect of chronic viral infection on epitope selection, cytokine production, and surface phenotype of CD8 T cells and the role of IFN-gamma receptor in immune regulation. J Immunol 2004, 172(3):1491-1500.
• [46]Bulgarini D, Scalzo S, Boccoli G, Petrini M, Quaranta MT, Camagna A, Isacchi G, Testa U, Peschle C: IL-6/BSF-2 selectively stimulates the GO----S progression of CD8+ lymphocytes. J Biol Regul Homeost Agents 1991, 5(1):23-33.
• [47]Thedrez A, de Lalla C, Allain S, Zaccagnino L, Sidobre S, Garavaglia C, Borsellino G, Dellabona P, Bonneville M, Scotet E, et al.: CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells. Blood 2007, 110(1):251-258.
• [48]Wilkinson B, Chen JY, Han P, Rufner KM, Goularte OD, Kaye J: TOX: an HMG box protein implicated in the regulation of thymocyte selection. Nat Immunol 2002, 3(3):272-280.
• [49]Srinivas S, Dai J, Eskdale J, Gallagher GE, Megjugorac NJ, Gallagher G: Interferon-lambda1 (interleukin-29) preferentially down-regulates interleukin-13 over other T helper type 2 cytokine responses in vitro. Immunology 2008, 125(4):492-502.
• [50]Lowenthal JW, Zubler RH, Nabholz M, MacDonald HR: Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature 1985, 315(6021):669-672.
• [51]Datta S, Sarvetnick NE: IL-21 limits peripheral lymphocyte numbers through T cell homeostatic mechanisms. PLoS One 2008, 3(9):e3118.
• [52]Salem ML, Diaz-Montero CM, El-Naggar SA, Chen Y, Moussa O, Cole DJ: The TLR3 agonist poly(I:C) targets CD8+ T cells and augments their antigen-specific responses upon their adoptive transfer into naïve recipient mice. Vaccine 2009, 27(4):549-557.
• [53]Apasov SG, Blackburn MR, Kellems RE, Smith PT, Sitkovsky MV: Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling. J Clin Invest 2001, 108(1):131-141.
• [54]Botstein D, White RL, Skolnick M, Davis RW: Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 1980, 32(3):314-331.
• [55]Liu J, Liu Y, Liu X, Deng HW: Bayesian Mapping of Quantitative Trait Loci for Multiple Complex Traits with the Use of Variance Components. The American Journal of Human Genetics 2007, 81:304-320.
• [56]Zhang Q, Hoeschele L: Multiple QTL mapping in outcross populations via residual maximum likelihood. Proc 6th World Congr Genet Appl Lives Prod 1998, 26:265-268.
• [57]Grignola FE, Hoeschele I, Tier B: Mapping quantitative trait loci in outcross populations via residual maximum likelihood. I. Methodology. Genetics Selection Evolution 1996, 28:479-490. BioMed Central Full Text
• [58]Churchill GA, Doerge RW: Empirical threshold values for quantitative trait mapping. Genetics 1994, 138(3):963-971.
• [59]Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society 1995, 57:289-300.