Abstract
Chronic viral hepatitis is characterized by a dramatic lymphocyte infiltrate in the liver. Although it is one of the most common chronic inflammatory diseases in humans, little information is available on the functional state of these intra-hepatic lymphocytes (IHL). To address this issue, we have optimized cytofluorimetric techniques to assess directly ex vivo the functions, dynamics and repertoires of IHL isolated from biopsies of patients with chronic hepatitis C. We estimate that 1% of the total body lymphocytes infiltrate the inflamed liver and find that, at variance with peripheral blood lymphocytes (PBL) isolated from the same patients, most IHL display an activated phenotype and produce Th1 type lymphokines when stimulated in vitro. Virtually all IHL are found in the G0/G1 state of the cell cycle, while a sizeable percentage of them is undergoing programmed cell death in vivo, as detected by the TUNEL assay performed on freshly isolated cells. In contrast again to PBL from the same patients, IHL show a preferential compartmentalization of NK and TCRγ/δ+ cells, and a remarkable (up to 20-fold) enrichment for Vα24+ T cells. Together our data suggest that in a liver injured by chronic hepatitis C, most IHL are pro-inflammatory activated cells which are highly enriched for effecters of innate resistance. These IHL do not undergo clonal expansion in the liver but rather display effector function and die in situ at a high rate, suggesting that maintenance of the IHL pool is dependent on continuous migration from extra-hepatic sites.
| Original language | English |
|---|---|
| Pages (from-to) | 3448-3455 |
| Number of pages | 8 |
| Journal | European Journal of Immunology |
| Volume | 28 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1998 |
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Keywords
- Apoptosis
- Chronic inflammation
- Hepatitis C
- Intra-hepatic lymphocyte
- Vα24 T cell
ASJC Scopus subject areas
- Immunology
Cite this
Dynamics of intra-hepatic lymphocytes in chronic hepatitis C : Enrichment for Vα24+ T cells and rapid elimination of effector cells by apoptosis. / Nuti, Sandra; Rosa, Domenico; Valiante, Nicholas M.; Saletti, Giulietta; Caratozzolo, Marcello; Dellabona, Paolo; Barnaba, Vincenzo; Abrignani, Sergio.
In: European Journal of Immunology, Vol. 28, No. 11, 11.1998, p. 3448-3455.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dynamics of intra-hepatic lymphocytes in chronic hepatitis C
T2 - Enrichment for Vα24+ T cells and rapid elimination of effector cells by apoptosis
AU - Nuti, Sandra
AU - Rosa, Domenico
AU - Valiante, Nicholas M.
AU - Saletti, Giulietta
AU - Caratozzolo, Marcello
AU - Dellabona, Paolo
AU - Barnaba, Vincenzo
AU - Abrignani, Sergio
PY - 1998/11
Y1 - 1998/11
N2 - Chronic viral hepatitis is characterized by a dramatic lymphocyte infiltrate in the liver. Although it is one of the most common chronic inflammatory diseases in humans, little information is available on the functional state of these intra-hepatic lymphocytes (IHL). To address this issue, we have optimized cytofluorimetric techniques to assess directly ex vivo the functions, dynamics and repertoires of IHL isolated from biopsies of patients with chronic hepatitis C. We estimate that 1% of the total body lymphocytes infiltrate the inflamed liver and find that, at variance with peripheral blood lymphocytes (PBL) isolated from the same patients, most IHL display an activated phenotype and produce Th1 type lymphokines when stimulated in vitro. Virtually all IHL are found in the G0/G1 state of the cell cycle, while a sizeable percentage of them is undergoing programmed cell death in vivo, as detected by the TUNEL assay performed on freshly isolated cells. In contrast again to PBL from the same patients, IHL show a preferential compartmentalization of NK and TCRγ/δ+ cells, and a remarkable (up to 20-fold) enrichment for Vα24+ T cells. Together our data suggest that in a liver injured by chronic hepatitis C, most IHL are pro-inflammatory activated cells which are highly enriched for effecters of innate resistance. These IHL do not undergo clonal expansion in the liver but rather display effector function and die in situ at a high rate, suggesting that maintenance of the IHL pool is dependent on continuous migration from extra-hepatic sites.
AB - Chronic viral hepatitis is characterized by a dramatic lymphocyte infiltrate in the liver. Although it is one of the most common chronic inflammatory diseases in humans, little information is available on the functional state of these intra-hepatic lymphocytes (IHL). To address this issue, we have optimized cytofluorimetric techniques to assess directly ex vivo the functions, dynamics and repertoires of IHL isolated from biopsies of patients with chronic hepatitis C. We estimate that 1% of the total body lymphocytes infiltrate the inflamed liver and find that, at variance with peripheral blood lymphocytes (PBL) isolated from the same patients, most IHL display an activated phenotype and produce Th1 type lymphokines when stimulated in vitro. Virtually all IHL are found in the G0/G1 state of the cell cycle, while a sizeable percentage of them is undergoing programmed cell death in vivo, as detected by the TUNEL assay performed on freshly isolated cells. In contrast again to PBL from the same patients, IHL show a preferential compartmentalization of NK and TCRγ/δ+ cells, and a remarkable (up to 20-fold) enrichment for Vα24+ T cells. Together our data suggest that in a liver injured by chronic hepatitis C, most IHL are pro-inflammatory activated cells which are highly enriched for effecters of innate resistance. These IHL do not undergo clonal expansion in the liver but rather display effector function and die in situ at a high rate, suggesting that maintenance of the IHL pool is dependent on continuous migration from extra-hepatic sites.
KW - Apoptosis
KW - Chronic inflammation
KW - Hepatitis C
KW - Intra-hepatic lymphocyte
KW - Vα24 T cell
UR - http://www.scopus.com/inward/record.url?scp=0031740004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031740004&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199811)28:11<3448::AID-IMMU3448>3.0.CO;2-5
DO - 10.1002/(SICI)1521-4141(199811)28:11<3448::AID-IMMU3448>3.0.CO;2-5
M3 - Article
C2 - 9842887
AN - SCOPUS:0031740004
VL - 28
SP - 3448
EP - 3455
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 11
ER -