The distribution of T lymphocyte subtypes in cases with different chronic liver disease

Yıl 2013, Cilt: 40 Sayı: 2, 250 - 253, 01.06.2013

Sevgi Kalkanlı Taş Fulya İlhan Hüseyin Ataseven İbrahim Halil Bahçecioğlu Nalan Mirzai

https://doi.org/10.5798/diclemedj.0921.2013.02.0264

Öz

Objective: Hepatitis B is an important infectious disease, which can cause severe chronic cirrhosis and hepatocellular carcinoma in 1-5 % of adult patients. Whereas, Hepatitis D is a defective virus infection that develops in people with HBsAg (+). It has been known that Hepatitis D virus has a cytopathic effect but the immune mechanisms which play a role in the development of this disease are still under investigation. Therefore, in this study it was aimed to investigate whether lymphocytes numbers change in a variety of patients with chronic hepatitis. Methods: In this study, 22 patients (12 females and 10 males) with chronic liver diseases were examined. These patients were compared to the control group which consists of 20 healthy individuals (12 females, 8 males). A flow cytometry assay was conducted to examine T lymphocyte subgroups using CD3, CD4, CD8, CD25, CD56, CD161 and Vα24 monoclonal antibodies in peripheral blood samples of both patient and control groups. Results: The mean age of patient group and control group were 45.87±11.18 and 41.45±7.23 year respectively. The HbsAg was found to be positive in all patients with the exception of one patient. 15 patients also exhibited Anti Delta Antigen positive as well as HbsAg. Six of these patients have been diagnosed with chronic liver disease, 7 of them have been diagnosed liver chrosis and two of them have been diagnosed with hepathoma. No difference was found between the patients and healthy controls in terms of total T lymphocyte, CD4+Th cells CD3+CD56+ NKT cells and Vα24+CD161+ iNKT cells. However, the levels of CD8+ Tc cells, CD16+56+ NK cells and CD4+CD25+ T lymphocytes were found to be lower in patients bloods as compared to the healthy controls. Conclusions: These results suggest that HbsAg positivity may cause the decreases of the cells which are responsible for cytotoxic response. Nevertheless, further studies are required to explain the immunological response to the chronic hepatitis.

Anahtar Kelimeler

Chronic hepatitis, total T lymphocyte, CD4+ T cell and CD3+CD56+ NKT.

Çeşitli kronik karaciğer hastalığı vakalarında T lenfosit subtiplerinin dağılımı

Öz

Amaç: Hepatit B erişkinlerde %1-5 oranında kronikleşebilen siroz ve hepatosellüler karsinomaya neden olabilen önemli bir enfeksiyon hastalığıdır. Hepatit D ise HBsAg (+) kişilerde gelişen bir enfeksiyondur. Hepatit D virüsünün sitopatik etkili olduğu bilinmektedir ancak bu hastalığın gelişiminde rol oynayan immün mekanizmalar halen araştırılmaktadır. Bundan dolayı, bu çalışmada çeşitli kronik hepatit vakalarında lenfositlerin sayısal değişikliği olup olmadığını araştırmak amaçlandı. Yöntemler: Bu çalışmada, kronik karaciğer hastalığı olan 12\'si kadın 10\'u erkek toplam 22 hasta değerlendirildi. Bu hastalar 12 kadın 8 erkekten oluşan, 20 kişilik sağlıklı kontrol grubu ile karşılaştırıldı. Hasta ve kontrol grubunun periferik kanlarında flow sitometrik yöntemle CD3, CD4, CD8, CD25, CD56, CD161 ve Vα24 monoklonal antikorları kullanılarak T lenfosit alt grupları araştırıldı. Bulgular: Hastaların ve kontrol grubunun yaş ortalaması sırasıyla 45.87±11.18 yıl, 41.45±7.23 yıl idi. Hastaların biri hariç tümünde, HBsAg pozitif olarak bulundu.15 hasta HBsAg yanı sıra Anti Delta pozitifliği de gösterdi. Bu hastaların; 6\'sı kronik karaciğer hastalığı, 7\'si karaciğer sirozu ve 2\'si ise hepatoma tanısı ile izlenmekteydi. Total T lenfosit, CD4+ Th hücre ve CD3+CD56+ NKT hücreler ve Vα24+CD161+ NKT hücreler açısından hasta ve kontrol grubu arasında fark saptanmadı. Ancak, CD8+ Tc, CD16+56+ NK hücreler ve CD4+CD25+ regülatör T hücre düzeylerinin, hastaların kanlarında kontrollere göre daha düşük olduğu saptandı. Sonuç: Bu sonuçlar, HBsAg pozitifliğinin sitotoksik yanıttan sorumlu hücrelerde ki azalmaya neden olduğunu ima etmektedir. Ancak kronik hepatitteki immünolojik cevabı açıklayabilmek için ileri çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

Kronik hepatit, total T lenfosit, CD4+ T hücre ve CD3+CD56+NKT.

Kaynakça

• Lucey DR, Clerol M, Shearer GM. Type I and type II cy- tokine dysregulation in human infections, neoplastic and inflammatory disease. Clin Microbiol Rev 1996;9:532-564.
• Milich DR, Schodel F, Hughes JL, et al. The hepatitis B virus core and e antigens elicit different Th cell phenotype. J Vi- rol 1997;71:2192-2201.
• Çınar K. Hepatit B Virusunun immunopatogenezi. Hepatit B ulusal uzlaşma toplantı metinleri 2004: sayfa 57-64.
• Boyer O, Saadoun D, Abriol J, et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryo- globulinemiavasculitis. Blood 2004;103:3428-3430.
• Furuichi Y,Tokuyama H, Ueha S, et al. Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization. World J Gastroenterol 2005;28:3772-3777.
• Durante-Mangoni E, Wang R, Shaulov A, et al. Hepatic CD1d expression in hepatitis C virus infection and recogni- tion by resi-dent proinflammatory CD1d-reactive T cells. J Immunol 2004;173:2159-2166.
• de Lalla C, Galli G, Aldrighetti L, et al. Production of pro- fibrotic cytokines by invariant NKT cells characterizes cir- rhosis pro-gression in chronic viral hepatitis. J Immunol 2004;173:1417-1425.
• Baron JL, Gardiner L, Nishimura S, et al. Activation of a nonclassical NKT cell subset in a transgenic mouse model of hepatitis B virus infection. Immunity 2002;16:583-594.
• Exley MA, He Q, Cheng O,et al. Cutting edge: Compartmen- talization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus infected liver. J Immunol 2002;168:1519- 1523.
• Deigman T, Curry MP, Doherty DG, et al. Decrease in he- patic CD56+ T cells and Vα24+ natural killer T cells in chronic hepatitis C virus infection. J Hepatol 2002;37:101- 108.
• Kawarabayashi N, Seki S, Hatsuse K, et al. Decrease of CD56+ T cells and natural killer cells in cirrhotic livers with hepatitis C may be involved in their susceptibility to hepatocellular carcinoma. Hepatology 2000;32: 962-969.
• Nuti S, Rosa D, Valiante N, et al. Dynamics of intra-hepatic lymphocytes in chronic hepatitis C: enrichment for Vα24+ T cells and rapid elimination of effector cells by apoptosis. Eur J Immunol 1998;28: 3448-3455.
• González LR, Conesa A, Blanca I, et al. Increased number of non-invariant NKT cells and low number of circulating CD1-expressing leukocytes in patients infected with hepa- titis C virus. Ann Biol Clin (Paris) 2012 ;70:695-701.
• Pawlotsky JM. Pathophysiology of hepatitis C virus infec- tion and related liver disease. TrendsMicrobiol 2004;12:96- 102.
• Okumura A, Ishikawa T, Maeno T, et al. Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma. Hepatol Res 2005;32:213-217.
• Swain MG. Natural killer T cells within the liver: conduc- tors of the hepatic immune orchestra. Dig Dis 2010;28:7- 13.
• Alter G, Jost S, Rihn S, et al. Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+NK cells in acute HCV infection may predict viral clearance. J Hepa- tology 2011;55;278-288.