Advances in Clinical and Experimental Medicine
2018, vol. 27, nr 7, July, p. 979–986
doi: 10.17219/acem/73734
Publication type: original article
Language: English
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The clinical importance of changes in Treg and Th17 lymphocyte subsets in splenectomized patients after spleen injury
1 2nd Department of General, Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University of Lublin, Poland
2 Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Poland
3 Department of Anesthesiology, Medical University of Lublin, Poland
4 Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Poland
Abstract
Background. Splenectomized patients are more prone to bacterial infections due to their immunocompromised status. Little is known about the role of T helper 17 (Th17) and T regulatory cells (Treg) in the immune system of patients after the removal of the spleen.
Objectives. The aim of the present study was to analyze possible changes in CD4+ lymphocyte T subsets, especially Treg and Th17, in patients who had undergone splenectomy.
Material and Methods. The study included a group of 67 male patients (41.74 ±16.22 years). All patients had undergone splenectomy because of spleen injury. Mean time elapsed from splenectomy to analysis was 9.1 ±4.6 years. Control samples were obtained from 20 male healthy volunteers. The percentages and absolute counts of Th17 and Treg were measured using the flow cytometry method.
Results. The analysis of the antibody titer against 23 serotypes of Streptococcus pneumoniae (S. pneumoniae) in the splenectomized patients revealed its elevated values compared to controls (p = 0.0016). Higher percentages and absolute counts of Treg cells were found in the splenectomized group vs controls (p < 0.000007). Lower percentages and absolute counts of the Th17 subset were found in the study group vs controls (p < 0.000002 and p < 0.00006, respectively). The Treg cell percentage was positively correlated with the antibody titer against S. pneumoniae (p < 0.02). Th17 cells were reversely correlated with the antibody titer (p < 0.004 and p < 0.001 for absolute counts and percentage values, respectively). The Th17 subset values were significantly lower in the splenectomized patients who reported a higher frequency of upper respiratory tract infections (URTI) (p < 0.0001). No correlations were found between the time elapsed since splenectomy and the Treg or Th17 cell values in the study group.
Conclusion. Splenectomy results in an important deterioration of the Treg/Th17 cell balance with a predominance of immunoregulatory Tregs, which can contribute to insufficient immune response to infection.
Key words
immune response, T helper 17 cells, T regulatory cells, splenectomy
References (28)
- Morris DH, Bullock FD. The importance of the spleen in resistance to infection. Ann Surg. 1919;70:513–521.
- Bessler H, Bergman M, Salman H, Beilin B, Djaldetti M. The relationship between partial splenectomy and peripheral leukocyte count. J Surg Res. 2004;122:49–53.
- Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect. 2001;7:657–660.
- Shatz DV. Vaccination practices among North American trauma surgeons in splenectomy for trauma. J Trauma. 2002;53:950–956.
- Aguilar RB, Keister KJ, Russell AC. Prevention of sepsis after splenectomy. Dimens Crit Care Nurs. 2010;29:65–68.
- Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378:86–97.
- Morgan TL, Tomich EB. Overwhelming post-splenectomy infection (OPSI): A case report and review of the literature. J Emerg Med. 2012; 43:758–763.
- Davies JM, Lewis MP, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PH. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen, prepared on behalf of the British Committee for Standards in Haematology by a working party of the Haemato-Oncology task force. Br J Haematol. 2011;155:308–317.
- Evans DI. Postsplenectomy sepsis 10 years or more after operation. J Clin Pathol. 1985;38:309–311.
- Torres A, Bonanni P, Hryniewicz W, Moutschen M, Reinert RR, Welte T. Pneumococcal vaccination: What have we learnt so far and what can we expect in the future? Eur J Clin Microbiol Infect Dis. 2015;34:19–31.
- Centers for Disease Control and Prevention (CDC). Recommended Adult Immunization Schedule – United States, 2016. www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule.pdf. Accessed February 25, 2016.
- Zandvoort A, Timens W. The dual function of the splenic marginal zone: Essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens. Clin Exp Immunol. 2002;130:4–11.
- Adeegbe D, Matsutani T, Yang J, Altman NH, Malek TR. CD4(+) CD25(+) Foxp3(+) T regulatory cells with limited TCR diversity in control of autoimmunity. J Immunol. 2010;184:56–66.
- Bonelli M, Savitskaya A, von Dalwigk K, et al. Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE). Int Immunol. 2008;20:861–868.
- Sempere-Ortells JM, Perez-Garcia V, Marin-Alberca G, et al. Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to disease activity score-28. Autoimmunity. 2009;42:636–645.
- Annunziato F, Cosmi L, Santarlasci V, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–1861.
- Wilson NJ, Boniface K, Chan JR, et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007;8:950–957.
- Afzali B, Lombardi G, Lechler RI, et al. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol. 2007;148:32–46.
- Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60: 1472–1483.
- Shao XS, Yang XQ, Zhao XD, et al. The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome. Ped Nephrol. 2009;24:1683–1690.
- Yu S, Liu C, Li L, et al. Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia. Lab Invest. 2015;95:157–167.
- Klatka M, Grywalska E, Partyka M, Charytanowicz M, Kiszczak-Bochynska E, Rolinski J. Th17 and Treg cells in adolescents with Graves’ disease: Impact of treatment with methimazole on these cell subsets. Autoimmunity. 2014;47:201–211.
- Grywalska E, Surdacka A, Miturski A, et al. Characterisation of lymphocyte subsets in asplenic patients: Preliminary report. Centr Eur J Immunol. 2010;35:239–244.
- Pasiarski M, Rolinski J, Grywalska E, et al. Antibody and plasmablast response to 13-valent pneumococcal conjugate vaccine in chronic lymphocytic leukemia patients: Preliminary report. PLoS One. 2014;9: e114966.
- Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: Mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531–564.
- Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441:235–238.
- Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13:668–677.
- Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531–562.