8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:213 (abstract no. 563)

Graham C, Curry M, He Q, Afdhal N, Nunes D, Koziel M; Beth Israel Deaconess Med Ctr.

BACKGROUND: Patients who are coinfected with HIV and HCV have an accelerated progression of liver disease compared to patients with HCV alone, but the mechanism is unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes. We examined intrahepatic cellular immune responses to HCV antigens (Ag) to determine whether there were quantitative differences in patients with and without HIV.

METHODS: Liver biopsies obtained from seven patients with chronic HCV and seven patients with HIV/HCV (median CD4 407, range 194-588) were cultured in the presence of IL-2 and a bispecific monoclonal antibody. Resultant expanded intrahepatic CD4-enriched cells were co-cultured with irradiated PBMC in the presence of HCV Ag Core, NS3, NS5, and PHA and a buffer control. Secretion of IFNgamma, TNFalpha and IL-10 was determined using ELISPOT assays. Averaged numbers of spot-forming cells in control wells were subtracted from Ag-stimulated wells. Median and intraquartile range (IQR) values were calculated for HIV/HCV and HCV groups and compared using the Mann-Whitney U test.

RESULTS: In our patients, there was no significant difference in liver biopsy grade or stage for HIV/HCV vs. HCV groups. In cells stimulated with Core, median HIV/HCV versus HCV secretion of IFNgamma was 0 (IQR 7.5) vs. 0 (IQR 318), TNFalpha was 0 (IQR 15) vs. (IQR 117) and IL-10 was 10 (IQR 28) vs. 47 (IQR 93); p>0.05. With NS3 stimulation of HIV/HCV vs. HCV cells, IFNgamma secretion was 0 (IQR 38) vs. 0 (IQR 118), TNFalpha was 48 (IQR 82) vs. 0 (IQR 80) and IL-10 was 0 (IQR 2) vs. 40 (IQR 158); p>0.05. With NS5 stimulation of HIV/HCV vs. HCV cells, IFNgamma secretion was 0 (IQR 10) vs. 0 (IQR 112) (p>0.05), TNFalpha 33 (IQR 98) vs. 50 (IQR 123) (p>0.05) and IL-10 0 (IQR 0) vs. 60 (IQR 168) (significant at p<0.01).

CONCLUSIONS: Wide variations in responses to HCV proteins by intrahepatic CD4-enriched cells were found for both HIV/HCV and HCV groups. No clear pattern of cytokine production was seen with HCV Ag stimulation for either group. This suggests that enhanced fibrosis observed in HIV/HCV is not due to a quantitative change in the immune response against HCV.

Keywords: AEGIS, Hepacivirus, HIV, Antigens, CD4, Cytokines, Hepatitis C Antigens, Antigens, HIV Infections, T-Lymphocytes, Interleukin-10, HIV Long-Term Survivors, Hepatitis Antigens, Human, AIDS

2001-02-04
563

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.