Intrahepatic and circulating HLA class II-restricted, hepatitis C virus-specific T cells: functional characterization in patients with chronic hepatitis C.
To compare the functional features of circulating and intrahepatic hepatitis C virus (HCV)-specific CD4+ T cells in chronic HCV infection, peripheral blood and liver-infiltrating lymphocytes from 29 patients with chronic hepatitis C were stimulated with structural and nonstructural HCV proteins to produce antigen-specific T-cell lines and clones. Antigen specificity, fine specificity, phenotype, cytokine production, and T-cell receptor (TCR)-vbeta chain expression were analyzed. The results indicate a hierarchy of stimulatory capacity by the different HCV proteins, core being the antigen most frequently recognized by CD4+ intrahepatic lymphocytes, followed by NS4 and NS5. The CD4 response was directed simultaneously against different HCV proteins in individual patients, but fine-specificity analysis indicated that the response was generally focused on a limited number of immunodominant epitopes. Although the narrowly focused nature of this response may favor the emergence of escape mutations, this event was not observed by following-up over time the sequence of 2 epitopes strongly immunodominant for intrahepatic CD4 cells of a patient with chronic HCV infection. In conclusion, simultaneous analysis of peripheral blood and intrahepatic CD4 cells in the same patients indicated a predominant Th1 profile of HCV-specific CD4 cells and suggests a specific compartmentalization of virus-specific T cells into the liver.
Penna
Amalia
A
Laboratorio di Immunopatologia Virale, Divisione Malattie Infettive, Azienda Ospedaliera di Parma, Parma, Italy.
Missale
Gabriele
G
Lamonaca
Vincenzo
V
Pilli
Massimo
M
Mori
Cristina
C
Zanelli
Paola
P
Cavalli
Albertina
A
Elia
Gianfranco
G
Ferrari
Carlo
C
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D012367:RNA, Viral / Q000032:analysis
D016207:Cytokines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008934:Mitogens; D012367:RNA, Viral