Browse > Article
http://dx.doi.org/10.5713/ajas.2012.12576

Association of the Porcine Cluster of Differentiation 4 Gene with T Lymphocyte Subpopulations and Its Expression in Immune Tissues  

Xu, Jingen (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Liu, Yang (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Fu, Weixuan (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Wang, Jiying (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Wang, Wenwen (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Wang, Haifei (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Liu, Jianfeng (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Ding, Xiangdong (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Zhang, Qin (Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University)
Publication Information
Asian-Australasian Journal of Animal Sciences / v.26, no.4, 2013 , pp. 463-469 More about this Journal
Abstract
Cluster of differentiation 4 (CD4) is mainly expressed on $CD4^+$ T cells, which plays an important role in immune response. The aim of this study was to detect the association between polymorphisms of the CD4 gene and T lymphocyte subpopulations in pigs, and to investigate the effects of genetic variation on the CD4 gene expression level in immune tissues. Five missense mutations in the CD4 gene were identified using DNA pooling sequencing assays, and two main haplotypes (CCTCC and AGCTG) in strong linkage disequilibrium (with frequencies of 50.26% and 46.34%, respectively) were detected in the population of Large White pigs. Our results indicated that the five SNPs and the two haplotypes were significantly associated with the proportions of $CD4^-CD8^-$, $CD4^+CD8^+$, $CD4^+CD8^-$, $CD4^+$ and $CD4^+/CD8^+$ in peripheral blood (p<0.05). Gene expression analysis showed the mRNA level of the CD4 gene in thymus was significantly higher than that in lymph node and spleen (p<0.05). However, no significant difference was observed between animals with CCTCC/CCTCC genotype and animals with AGCTG/AGCTG genotype in the three immune tissues (p>0.05). These results indicate that the CD4 gene may influence T lymphocyte subpopulations and can be considered as a candidate gene affecting immunity in pigs.
Keywords
Pig; CD4; Polymorphisms; T lymphocyte subpopulations; Expression;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Vignali, D. A., J. Moreno, D. Schiller and G. J. Hammerling. 1992. Species-specific binding of CD4 to the $\beta2$ domain of major histocompatibility complex class II molecules. J. Exp. Med. 175:925-932.   DOI   ScienceOn
2 Vignali, D. A. and J. L. Strominger. 1994. Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor. J. Exp. Med. 179:1945-1956.   DOI
3 Vignali, D. A. and K. M. Vignali. 1999. Profound enhancement of T cell activation mediated by the interaction between the TCR and the D3 domain of CD4. J. Immunol. 162:1431-1439.
4 Wang, J. H., R. Meijers, Y. Xiong, J. H. Liu, T. Sakihama, R. Zhang, A. Joachimiak and E. L. Reinherz. 2001. Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc. Natl. Acad. Sci. USA. 98:10799-10804.   DOI   ScienceOn
5 Wang, L., J. Fan, M. Yu, S. Zheng and Y. Zhao. 2011. Association of goat (Capra hircus) CD4 gene exon 6 polymorphisms with ability of sperm internalizing exogenous DNA. Mol. Biol. Rep. 38:1621-1628.   DOI
6 Wyatt, R., M. Thali, S. Tilley, A. Pinter, M. Posner, D. Ho, J. Robinson and J. Sodroski. 1992. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region. J. Virol. 66:6997-7004.
7 Zamani, M., M. A. Tabatabaiefar, S. Mosayyebi, A. Mashaghi and P. Mansouri. 2010. Possible association of the CD4 gene polymorphism with vitiligo in an Iranian population. Clin. Exp. Dermatol. 35:521-524.
8 Zerbib, A. C., A. B. Reske-Kunz, P. Lock and R. P. Sekaly. 1994. CD4-mediated enhancement or inhibition of T cell activation does not require the CD4: $p56^{lck}$ association. J. Exp. Med. 179:1973-1983.   DOI
9 Feng, W. H., M. B. Tompkins, J. S. Xu, T. T. Brown, S. M. Laster, H. X. Zhang and M. B. McCaw. 2002. Thymocyte and peripheral blood T lymphocyte subpopulation changes in piglets following in utero infection with porcine reproductive and respiratory syndrome virus. Virology 302:363-372.   DOI   ScienceOn
10 Fleury, S., B. Huang, A. Zerbib, G. Croteau, E. O. Long and R. P. Sekaly. 1996. Mutations in human CD4 impair the functional interaction with different human and mouse class II isotypes and alleles. J. Immunol. 156:1848-1855.
11 Gustafsson, K., S. Germana, T. M. Sundt, D. H. Sachs and C. LeGuern. 1993. Extensive allelic polymorphism in the CDR2-like region of the miniature swine CD4 molecule. J. Immunol. 151:1365-1370.
12 He, Y., Q. Chu, P. Ma, Y. Wang, Q. Zhang, D. Sun, Y. Zhang, Y. Yu and Y. Zhang. 2011. Association of bovine CD4 and STAT5b single nucleotide polymorphisms with somatic cell scores and milk production traits in Chinese Holsteins. J. Dairy Res. 78:242-249.   DOI   ScienceOn
13 Kristiansen, O. P., A. E. Karlsen, Z. M. Larsen, J. Johannesen, F. Pociot and T. Mandrup-Poulsen. 2004. Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity. Scand. J. Immunol. 59:582-591.   DOI   ScienceOn
14 Lee, K. M., D. Baris, Y. Zhang, H. D. Hosgood, I. Menashe, M. Yeager, S. H. Zahm, S. S. Wang, M. P. Purdue, S. Chanock, T. Zheng, N. Rothman and Q. Lan. 2010. Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut. Am. J. Hematol. 85:560-563.   DOI   ScienceOn
15 Livak, K. J. and T. D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C(T)) method. Methods 25:402-408.   DOI   ScienceOn
16 Lu, X., J. F. Liu, Y. F. Gong, Z. P. Wang, Y. Liu and Q. Zhang. 2011. Mapping quantitative trait loci for T lymphocyte subpopulations in peripheral blood in swine. BMC. Genet. 12:79.
17 Summerfield, A., H. J. Rziha and A. Saalmuller. 1996. Functional characterization of porcine $CD4^{+}CD8^{+}$ extrathymic T lymphocytes. Cell. Immunol. 168:291-296.   DOI   ScienceOn
18 Zhou, C., Z. Liu, J. Jiang, Y. Yu and Q. Zhang. 2012. Differential gene expression profiling of porcine epithelial cells infected with three enterotoxigenic Escherichia coli strains. BMC Genomics 13:330.   DOI
19 Shaw, A. S., J. Chalupny, J. A. Whitney, C. Hammond, K. E. Amrein, P. Kavathas, B. M. Sefton and J. K. Rose. 1990. Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the $p56^{lck}$ tyrosine protein kinase. Mol. Cell. Biol. 10:1853-1862.
20 Strong, J., Q. Wang and N. Killeen. 2001. Impaired survival of T helper cells in the absence of CD4. Proc. Natl. Acad. Sci. USA. 98:2566-2571.   DOI   ScienceOn
21 Sundt, T. M., C. LeGuern, S. Germana, C. V. Smith, K. Nakajima, J. K. Lunney and D. H. Sachs. 1992. Characterization of a polymorphism of CD4 in miniature swine. J. Immunol. 148:3195-3201.
22 Vasilopoulos, Y., M. J. Cork, D. Teare, I. Marinou, S. J. Ward, G. W. Duff and R. Tazi-Ahnini. 2007. A nonsynonymous substitution of cystatin A, a cysteine protease inhibitor of house dust mite protease, leads to decreased mRNA stability and shows a significant association with atopic dermatitis. Allergy 62:514-519.   DOI   ScienceOn
23 Boscariol, R., J. Pleasance, D. M. Piedrafita, H. W. Raadsma and T. W. Spithill. 2006. Identification of two allelic forms of ovine CD4 exhibiting a $Ser^{183}/Pro^{183}$ polymorphism in the coding sequence of domain 3. Vet. Immunol. Immunopathol. 113:305-312.   DOI   ScienceOn
24 Appleyard, G. D., S. E. Furesz and B. N. Wilkie. 2002. Blood lymphocyte subsets in pigs vaccinated and challenged with Actinobacillus pleuropneumoniae. Vet. Immunol. Immunopathol. 86:221-228.   DOI   ScienceOn
25 Banda, N. K., J. Bernier, D. K. Kurahara, R. Kurrle, N. Haigwood, R. P. Sekaly and T. H. Finkel. 1992. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. J. Exp. Med. 176:1099-1106.   DOI   ScienceOn
26 Barber, E. K., J. D. Dasgupta, S. F. Schlossman, J. M. Trevillyan and C. E. Rudd. 1989. The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase ($p56^{lck}$) that phosphorylates the CD3 complex. Proc. Natl. Acad. Sci. USA. 86:3277-3281.   DOI   ScienceOn
27 Charerntantanakul, W. and J. A. Roth. 2006. Biology of porcine T lymphocytes. Anim. Health. Res. Rev. 7:81-96.   DOI   ScienceOn
28 Chen, J., B. K. Lipska, N. Halim, Q. D. Ma, M. Matsumoto, S. Melhem, B. S. Kolachana, T. M. Hyde, M. M. Herman, J. Apud, M. F. Egan, J. E. Kleinman and D. R. Weinberger. 2004. Functional analysis of genetic variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain. Am. J. Hum. Genet. 75:807-821.   DOI   ScienceOn
29 Doyle, C. and J. L. Strominger. 1987. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 330:256-259.   DOI   ScienceOn
30 Fabbri, M., C. Smart and R. Pardi. 2003. T lymphocytes. Int. J. Biochem. Cell. Biol. 35:1004-1008.   DOI   ScienceOn
31 Moldovan, M. C., A. Yachou, K. Levesque, H. Wu, W. A. Hendrickson, E. A. Cohen and R. P. Sekaly. 2002. CD4 dimers constitute the functional component required for T cell activation. J. Immunol. 169:6261-6268.   DOI
32 Maekawa, A., B. Schmidt, B. Fazekas de St Groth, Y. H. Sanejouand and P. J. Hogg. 2006. Evidence for a domain-swapped CD4 dimer as the coreceptor for binding to class II MHC. J. Immunol. 176:6873-6878.   DOI
33 Maroto, R., X. Shen and R. Konig. 1999. Requirement for efficient interactions between CD4 and MHC class II molecules for survival of resting $CD^{+}$ T lymphocytes in vivo and for activation-induced cell death. J. Immunol. 162:5973-5980.
34 Moebius, U., P. Pallai, S. C. Harrison and E. L. Reinherz. 1993. Delineation of an extended surface contact area on human CD4 involved in class II major histocompatibility complex binding. Proc. Natl. Acad. Sci. USA. 90:8259-8263.   DOI
35 Neff, M. M., E. Turk and M. Kalishman. 2002. Web-based primer design for single nucleotide polymorphism analysis. Trends Genet. 18:613-615.   DOI   ScienceOn
36 Pauly, T., M. Konig, H. J. Thiel and A. Saalmuller. 1998. Infection with classical swine fever virus: effects on phenotype and immune responsiveness of porcine T lymphocytes. J. Gen. Virol. 79:31-40.
37 Perez-Diez, A., N. T. Joncker, K. Choi, W. F. Chan, C. C. Anderson, O. Lantz and P. Matzinger. 2007. CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood 109:5346-5354.   DOI   ScienceOn
38 Saalmuller, A., W. Hirt and M. J. Reddehase. 1989. Phenotypic discrimination between thymic and extrathymic $CD4^{-}$$CD8^{-}$ and $CD4^{+}$$CD8^{+}$ porcine T lymphocytes. Eur. J. Immunol. 19:2011-2016.   DOI   ScienceOn
39 Segales, J., F. Alonso, C. Rosell, J. Pastor, F. Chianini, E. Campos, L. Lopez-Fuertes, J. Quintana, G. Rodriguez-Arrioja, M. Calsamiglia, J. Pujols, J. Dominguez and M. Domingo. 2001. Changes in peripheral blood leukocyte populations in pigs with natural postweaning multisystemic wasting syndrome (PMWS). Vet. Immunol. Immunopathol. 81:37-44.   DOI   ScienceOn