Depletion of CD8+ T lymphocytes by murine monoclonal CD8 antibodies and restored specific T cell proliferation in vivo in a patient with chronic hepatitis C.
Cellular immune mechanisms, especially those mediated by CD8+ T cells, are important in the pathogenesis and control of viral infections. On the other hand, as shown for chronic lymphocytic choriomeningitis virus infection in the mouse, CD8+ T cells may not only hinder the elimination of a virus, but make the host unresponsive to a second viral infection. In hepatitis C virus (HCV) infections, at least 50% of the patients become chronically infected, despite the detection of HCV-specific CTL and a specific proliferative response to HCV Ags in PBL and in lymphocytes isolated from the liver. To better understand the immunopathologic mechanisms of CD8+ cells in vivo and to search for a potential treatment, we applied murine CD8 mAbs to a patient with therapy-resistant chronic HCV. A drastic reduction of CD8+ circulating lymphocytes, a reduction of CD8 molecule density, and complement fixation on CD8+ cells were observed. The reduction of CD8+ cells was compensated partially by an elevation of CD4+ cells. High concentrations of neutralizing human anti-mouse Abs were induced. After the Ab infusions, the CD4/CD8 ratio in peripheral blood increased from 1.6 to values of about 3 during therapy, and gradually decreased to 2.3 1 yr after the last mAb infusion. A continuing decrease of serum aminotransferases and clinical improvement was observed. Interestingly, after initiation of treatment, a significant proliferative response to HCV-specific Ags became measurable.
Kiefersauer
S
S
Institute for Immunology, Klinikum Grosshadern, University of Munich, Germany.
Reiter
C
C
Eisenburg
J
J
Diepolder
H M
HM
Rieber
E P
EP
Riethmüller
G
G
Gruber
R
R
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D016827:CD8 Antigens / Q000097:blood / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003168:Complement Fixation Tests; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000097:blood; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D016827:CD8 Antigens; D012367:RNA, Viral; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase