Differential expansion of T-cell receptor variable beta subsets after antigenic stimulation in patients with different outcomes of hepatitis C infection.
Persistent antigenic stimulation during chronic hepatitis C may alter the T-cell receptor variable chain beta (TCR BV) repertoire as well as the cytokine responses of hepatitis C virus (HCV)-specific T lymphocytes. We analysed the distribution of the TCR BV subsets 2.1, 3.1, 5.1, 6.1, 8, 13.1, 13.6, 14.1, 17.1, 21.3 in relation to intracytoplasmic expression of interleukin-2, interferon-gamma, interleukin-4 and interleukin-10. Using flow cytometry, CD45RO+ memory T cells of 27 patients with chronic hepatitis C, eight patients with resolved HCV infection and 16 non-HCV-related controls were studied with and without stimulation by the HCV core, NS3, NS4, NS5a and NS5b proteins. Patients with chronic and resolved hepatitis C differed by larger basal TCR BV2.1+, BV6.1+, BV17.1+ and BV21.3+ subsets in chronic hepatitis C, which were correlated to the numbers of T cells with spontaneous interleukin-2 and interferon-gamma production (r=0.51-0.73, P<0.05). Upon HCV-specific stimulation these subsets did not expand, whereas a marked in vitro expansion of TCR BV8+ T cells in response to all HCV proteins was selectively noted in chronic hepatitis C (P<0.05). This expansion of TCR BV8+ memory T cells was significantly correlated to HCV-induced interleukin-10 expression (r=0.58-0.98, P<0.01). Thus, differential involvement of selected TCR BV subsets may be related to the outcome of HCV infection.
Woitas
Rainer P
RP
Department of Internal Medicine, University of Bonn, Germany. Woitas@uni-bonn.de
Sippel
Martin
M
Althausen
Eva-Maria
EM
Brackmann
Hans H
HH
Kochan
Bettina
B
Matz
Bertfried
B
Rockstroh
Jürgen K
JK
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D018936:Hepatitis C Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta