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Abstract         Curriculum          Bibliografia  
 
Since 1963 more than 30.000 orthotopic liver transplantation (OLT) have been performed all over the world.  
OLT is now no more an experimental therapy but an estabilished therapeutic intervention for a wide variety of diseases and as the success of the operation has improved, the indications for liver transplant have expanded. 
Liver transplantation has profoundly altered the otherwise fatal outcome for patients with end-stage liver disease. 
Recently, the group of Doctor O.Cuomo et al. at Hospital Cardarelli of Naples has performed the first liver transplant using a novel immunological methodology in collaboration of the group of Doctor O.Perrella et al. 
Immunological laboratory variables included: 

-Monitoring of immune response 
-Analysis of V beta T lymphocyte repertoire 
-Th1 and Th2 cytokine expression 
-Phenotypic analysis of different T cell subsets 

 

Despite recent advances in the knowledge of the molecular virology of HCV, its pathogenesis is still unclear. Immunohistochemical studies have shown that the intrahepatic infiltrate cells consist mainly of activated CD8+ and CD4+ T cells.  
On this basis, it is likely that cellular immune response might play an important pathogenetic role.  
Recent studies have demonstrated that CD4+CD7+ and CD4+CD7-T cells define a CD4+Th cell subset with a Th1 or Th2 like profile of cytokine secretion respectively.  
The discovery that this subset can determine a preferential cytokine pattern has inspired the present study.  
Therefore, we have evaluated this subset and its correlation to activated CD8+T lymphocytes in both liver and peripheral blood of twenty consecutive patients with hepatisis C infection defined as 
 
 
 

 chronic on the basis of elevated serum aminotransferase levels for at least 6 months and after histologic study according to the criteria of Knodell. 
No patient had received any antiviral therapy before being entered into this study and all were seronegative for both hepatisis B virus and HIV markers.  
All patients gave informed  written consent and this study was approved by local ethics committee.  
Viral quantitation and HCV genotype were obtained according to the current methods. 
Each hepatic tissue obtained from liver biopsy  was processed for at least 4 minutes with semiautomatic disintegrator (Medimachine, Dako) that operates at a constant speed of about 100 rpm., so that tissue is disintegrated without trauma into single cells suspensions and analyzed with a flow cytometer (Ortho Diagnostic) according to a standard procedure.  
For the analysis of T cell subsets we have utilized monoclonal antibodies (Ortho Diagnostic) in two colours (FITC+PE). Our data showed that there was a higher expression of both CD4+CD7+ and CD8+CD38+ in liver than blood of patients with a more severe histologic forme (Knodell median 9.5) (p<0.001). 
Particularly, there was a significant correlation between liver CD4+CD7+ and CD8+CD38+ and alanine aminotransferase (p<0.01) and viral quantitation (p<0.05).  
No significant difference was present between CD4+CD7+ or CD8+CD38+ levels and HCV genotype.  
Conversely, in the patients with a moderate histologic grading (Knodell median, 3) there was an inverse T lymphocyte pattern: a lower expression of both CD4+CD7+ and CD8+CD38+ was present in liver than in blood (p<0.01). 
Our data seem support the hypothesis that: 
a) CD4+CD7+T cells seem induce a mediation in hepatic damage; 
b) CD4+CD7+T cells can contribute to CD8+CD38+ activity in the liver; 
c) A higher level of both CD4+CD7+ and CD8+CD38+ in the blood than liver seems relate to a minor histologic activity. 
The fact that CD4+CD7+T cells secrete Th1 cytokines (4) also suggests that its compartmentalization in the liver and a contemporary expansion in the blood of CD4+CD7-T cells with Th2/Th0 cytokine profile support the hypothesis that Th1-like cytokines and, particularly, a balance between Th1 and Th2 immune response may play a possible important role in the pathogenesis and develop of chronic hepatisis C virus related.  
This seems in agreement with other human diseases such as HIV infection in which a similar pattern of T cells characterize the Lymphoid tissue and blood. 

Oreste Perrella*, Oreste Cuomo** 

* Settore Immunologia delle Infezioni- III Div. Sez 3/4-Ospedale D.Cotugno 
** Chirurgia Laparoscopica specialistica epatica e Centro Trapianti Epatici-Osp. A.Cardarelli
 
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