Pediatric Nephrology

, 25:119 | Cite as

Zeta chain expression in T and NK cells in peripheral blood of children with nephrotic syndrome

  • Kinga Musiał
  • Lidia Ciszak
  • Agata Kosmaczewska
  • Aleksandra Szteblich
  • Irena Frydecka
  • Danuta Zwolińska
Original Article


The idiopathic nephrotic syndrome (INS) has been related to cellular immune disturbances. The zeta (ζ) chain, a component of the T-cell receptor/CD3 (TCR) complex and CD16 heterodimer in NK cells, plays a crucial role in T and NK cell activation and proliferation. The aim of our study was to examine zeta chain expression in CD4+, CD8+ T lymphocytes and NK cells in the peripheral blood of children with INS and to evaluate the effect of anti-CD3+rIL-2 stimulation on the level of zeta chain expression in the INS pediatric population. The study group consisted of 15 children with INS in relapse, 16 patients with INS in clinical remission, and 17 controls. The percentage of zeta-positive cells and the values of mean fluorescence intensity (MFI) were determined by flow cytometry. Compared with that in the controls, the percentage of zeta+ freshly isolated NK cells in children with INS in relapse was significantly lower, whereas, in CD3+/CD4+ and CD3+/CD8+ populations, no alteration was observed. There were no differences in the MFI values between the populations of freshly isolated cells either. Stimulation with anti-CD3+rIL-2 decreased the percentage of zeta+/CD4+ T cells and NKzeta+ cells in a significant way in all the groups analysed, whereas the percentage of zeta+/CD8+ T cells decreased significantly only in patients with INS in relapse. The altered pattern of zeta expression in fresh NK cells from children with INS in relapse, and the disturbed response of zeta+/CD8+ T cells to anti-CD3+rIL-2 stimulation in relapse, suggests the possible role of this chain in immune dysregulation in INS, particularly with regard to cytotoxic cells.


Idiopathic nephrotic syndrome Children T lymphocyte NK cell Zeta chain (ζ) Immune response 



The project was financed by the State Committee for Scientific Research (grant no. 2PO5E 055 26).


  1. 1.
    Cunard R, Kelly CJ (2002) T cells and minimal change disease. J Am Soc Nephrol 13:1409–1411CrossRefPubMedGoogle Scholar
  2. 2.
    Kaneko K, Tuchiya K, Fujinaga S, Kawamura R, Ohmoto Y, Shimizu T, Yamashiro Y (2002) Th1/Th2 balance in childhood idiopathic nephrotic syndrome. Clin Nephrol 58:393–397PubMedGoogle Scholar
  3. 3.
    Stachowski J, Barth C, Michalkiewicz J, Krynicki T, Jarmoliński T, Runowski D, Lewandowska-Stachowiak M, Zaniew M, Warzywoda A, Bortkiewicz E, Dobosz M, Maciejewski J, Baldamus CA (2000) Th1/Th2 balance and CD45-positive T cell subsets in primary nephritic syndrome. Pediatr Nephrol 14:779–785CrossRefPubMedGoogle Scholar
  4. 4.
    Daniel V, Trautmann Y, Konrad M, Nayir A, Scharer K (1997) T-lymphocyte populations, cytokines and other growth factors in serum and urine of children with idiopathic nephrotic syndrome. Clin Nephrol 47:289–297PubMedGoogle Scholar
  5. 5.
    Yan K, Nakahara K, Awa S, Nishibori Y, Nakajima N, Kataoka S, Maeda M, Watanabe T, Matsushima S, Watanabe N (1998) The increase of memory T cell subsets in children with idiopathic nephrotic syndrome. Nephron 79:274–278CrossRefPubMedGoogle Scholar
  6. 6.
    Tomizawa S, Suzuki S, Oguri M, Kuroume T (1979) Studies of T lymphocyte function and inhibitory factors in minimal change nephrotic syndrome. Nephron 24:179–182CrossRefPubMedGoogle Scholar
  7. 7.
    Zachwieja J, Dworacki G, Bobkowski W, Dobrowolska-Zachwieja A, Zaniew M, Maciejewski J (2002) Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome. Pediatr Nephrol 17:197–200CrossRefPubMedGoogle Scholar
  8. 8.
    Ciszak L, Pawlak E, Kosmaczewska A, Potoczek S, Frydecka I (2007) Alterations in the expression of signal transducing CD3ζ chain in T cells from patients with chronic inflammatory and autoimmune diseases. Arch Immunol Ther Exp (Warsz) 55:373–386CrossRefGoogle Scholar
  9. 9.
    Irving BA, Chan AC, Weiss A (1993) Functional characterization of signal transducing motif present in the T cell antigen receptor zeta chain. J Exp Med 177:1093–1103CrossRefPubMedGoogle Scholar
  10. 10.
    Frank SJ, Niklinska BB, Orloff DG, Mercep M, Ashwell JD, Klausner RD (1990) Structural mutations of the T cell receptor zeta chain and its role in T cell activation. Science 249:174–177CrossRefPubMedGoogle Scholar
  11. 11.
    Tsuzaka K, Nozaki K, Kumazawa C, Shiraishi K, Setoyama Y, Yoshimoto K, Abe T, Takeuchi T (2006) TCR ζ mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patients. Springer Semin Immunopathol 28:185–193CrossRefPubMedGoogle Scholar
  12. 12.
    Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC (2005) Increased caspase-3 expression and activity contribute to reduced CD3ζ expression in systemic lupus erythematosus T cells. J Immunol 175:3417–3423PubMedGoogle Scholar
  13. 13.
    Solomou EE, Wong S, Visconte V, Gibellini F, Young NS (2007) Decreased TCR ζ-chain expression in T cells from patients with acquired aplastic anaemia. Br J Haematol 138:72–76CrossRefPubMedGoogle Scholar
  14. 14.
    Rieux-Laucat F, Hivroz C, Lim A, Mateo V, Pellier I, Selz F, Fischer A, Le Deist F (2006) Inherited and somatic CD3 ζ mutations in a patient with T-cell deficiency. N Engl J Med 354:1913–1921CrossRefPubMedGoogle Scholar
  15. 15.
    Roberts JL, Lauritsen JPH, Cooney M, Parrott RE, Sajaroff EO, Win CM, Keller MD, Carpenter JH, Carabana J, Krangel MS, Sarzotti M, Zhong XP, Wiest DL, Buckley RH (2007) T B+ NK+ severe combined immunodeficiency caused by complete deficiency of the CD3ζ subunit of the T-cell antigen receptor complex. Blood 109:3198–3206CrossRefPubMedGoogle Scholar
  16. 16.
    Musiał K, Ciszak L, Kosmaczewska A, Szteblich A, Pawlak E, Zwolińska D, Frydecka I (2006) Expression of zeta chain in peripheral blood T lymphocytes and NK cells of children with idiopathic nephrotic syndrome—preliminary results. Przegl Lek 63:208–210PubMedGoogle Scholar
  17. 17.
    Aviles DH, Vehaskari MV, Culotta KS, Manning J, Ochoa AC, Zea AH (2009) T cell CD3 receptor zeta (TCRζ)-chain expression in children with idiopathic nephrotic syndrome. Pediatr Nephrol 24:769–773CrossRefPubMedGoogle Scholar
  18. 18.
    International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 98:561–564CrossRefGoogle Scholar
  19. 19.
    Bronstein-Sitton N, Wang L, Cohen L, Baniyash M (1999) Expression of the T cell antigen receptor ζ chain following activation is controlled at distinct checkpoints. J Biol Chem 274:23659–23665CrossRefPubMedGoogle Scholar
  20. 20.
    Berg L, Roennelid J, Klareskog L, Bucht A (2000) Down-regulation of the T cell receptor CD3zeta chain in rheumatoid arthritis (RA) and its influence on T cell responsiveness. Clin Exp Immunol 120:174–182CrossRefPubMedGoogle Scholar
  21. 21.
    Migliorati G, Bartoli A, Nocentini G, Ronchetti S, Moraca R, Riccardi C (1997) Effect of dexamethasone on T-cell receptor/CD3 expression. Mol Cell Biochem 167:135–144CrossRefPubMedGoogle Scholar
  22. 22.
    Ravetch JV, Kinet JP (1991) Fc receptors. Annu Rev Immunol 9:457–492PubMedGoogle Scholar
  23. 23.
    Krishnan S, Warke VG, Nambiar MP, Wong HK, Tsokos GC, Farber DL (2003) The FcRγ subunit and Syk kinase replace the CD3ζ-chain and Zap-70 kinase in the TCR signaling complex of human effector CD4 T cells. J Immunol 170:4189–4195PubMedGoogle Scholar
  24. 24.
    Enyedy EJ, Nambiar MP, Liossis SN, Dennis G, Kammer GM, Tsokos GC (2001) Fc epsilon receptor type I gamma chain replaces the deficient T cell receptor zeta chain in T cells of patients with systemic lupus erythematosus. Arthritis Rheum 44:1114–1121CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2009

Authors and Affiliations

  • Kinga Musiał
    • 1
  • Lidia Ciszak
    • 2
  • Agata Kosmaczewska
    • 2
  • Aleksandra Szteblich
    • 2
  • Irena Frydecka
    • 2
  • Danuta Zwolińska
    • 1
  1. 1.Department of Pediatric NephrologyWrocław Medical UniversityWrocławPoland
  2. 2.Laboratory of Immunopathology, Institute of Immunology and Experimental TherapyPolish Academy of SciencesWrocławPoland

Personalised recommendations