Clonotypic analysis of T cells in patients with autoimmune and viral hepatitis

Abstract

It is known that T cells recognize an antigen via the T-cellThe immunopathogenesis of autoimmune hepatitis receptor (TCR). Antigen-specificity of a T cell depends on the (AIH), and the role of T cells in the onset and mainte-TCR, particularly the nucleotide sequences in the complenance of this disease, are still unclear. Since T cells exmentarity-determining region 3 (CDR3) of the TCR, which is pand clonally after stimulation by an antigen, it is improbably the direct recognition site for the antigen in the portant to analyze the behavior of T cells at a clonal context of major histocompatibility complex molecule. 3-5 Durlevel. We have established recently a novel system, using ing the antigen-specific immune response, T cells that bear reverse transcriptase-polymerase chain reaction (RTthe same sequence in the CDR3 would be selected, stimu-PCR) and subsequent single-strand conformation polylated, and expanded by a specific antigen. Consequently, an morphism (SSCP) that allows the identification of clonal accumulated clone is formed eliciting various immunological accumulation of T cells in a lymphocyte population. Useffects, including cytotoxicity or helper activity, in an antiing this system, we demonstrated that oligoclonal T cells gen-specific manner. Thus, it is crucial to investigate T-cell were accumulated in the liver of patients with AIH, and immunity at a clone level. It is possible at the present time that identical T-cell clonotypes were detected in two difto detect certain T-cell clonotypes within a heterogeneous ferent regions of the liver, although these features were population based on differences in nucleotide sequence of the also observed in cases with viral hepatitis. Only in cases CDR3 of the TCR transcripts. We have recently described with AIH, however, nearly all identical T cells were a novel method of T-cell clonotype analysis to study T-cell found to belong to CD8 / subset and there were very few immunity, using a combination of reverse-transcriptase poly-CD4 / T cells in this population. Our results suggest that merase chain reaction (RT-PCR) with multiple TCR primers common antigens presented to CD8 / T cells in the conand subsequent single-strand conformation polymorphism. 6 text of HLA class I molecule are distributed diffusely inThis method allows us to analyze T-cell populations at a the liver of AIH. These findings also suggest that anticlonal level, and to eliminate the bias associated with gens recognized by CD4 / T cells may be relatively hetartifacts in the process of establishing T-cell clones in vitro. 7-11 erogeneous in the liver with AIH. (HEPATOLOGY 1997;Using this RT-PCR/SSCP system, we investigated T-cell clon-25:1070-1076.) ality in the liver of six patients with AIH. We demonstrated a generalized accumulation of CD8 / T-cell clonotypes in the Autoimmune hepatitis (AIH) is a chronic liver disease char-liver, suggesting a universal distribution of the antigens elicacterized by a persistent inflammatory reaction in the liver. iting T-cell activation in the liver. Howeve...

Peripheral CD8+/CD25+ lymphocytes may be implicated in hepatocellular injuries in patients with acute-onset autoimmune hepatitis

“…1 The involvement of CD8ϩ lymphocytes in the pathogenesis of AIH is increasingly be coming obvious. 9,10 It appears that swift and extensive damage to hepatocytes in the initial stage of AIH would be mediated by CTL through the major histocompatibility (MHC) class 1 pathway. As AIH becomes full-blown, hepatitis would tend to be mediated by helper T cells through the MHC class 2 pathway.…”

Analysis of T-cell repertoire in hepatitis-associated aplastic anemia

“…We have observed no increased association of HLA-DR2 in HAA patients. Differences in T-cell repertoire have been observed in other immune-mediated diseases, such as multiple sclerosis, 38,39 rheumatoid arthritis, 40,41 and autoimmune hepatitis, 42 where a limited number of T cells using a restricted diversity of the V ␤ subfamilies to proliferate dominantly is revealed in different patients, 21 but the TCR repertoire pattern is different among these diseases owing to the different antigenic triggers. 39,43,44 In summary, we show that in HAA there is an infiltration of both clonal and many nonclonal T cells, giving rise to a markedly skewed T-cell repertoire, as seen in both viral and autoimmune hepatitis.…”

Molecular Characterization of the T Cell Repertoire Using Immuno-scope Analysis and its Possible Implementation in Clinical Practice

“…Although we have covered in detail only RA and MS, immunoscope analysis will contribute to our understanding of other diseases as well, including autoimmune hepatitis [67][68][69][70], primary biliary cirrhosis [71][72][73], diabetes and psoriasis [74,75]. As was the case for RA and MS, candidate autoantigens have been proposed for these diseases as well [76][77][78][79].…”