Graham C, Curry M, Fleming C, Craven D, Cheney C, Koziel M; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 213 (abstract no. 564).
Beth Israel Deaconess Med Ctr.
Background: Patients coinfected with HIV and HCV are at increased risk for progression to cirrhosis compared with HCV-monoinfected patients. In people with chronic HCV, low-level HCV-specific T cells are present in peripheral blood mononuclear cells (PBMC). Most previous reports have focused on IFNgamma production. We hypothesized that there are immune-mediated differences in response to hepatitis C in patients with and without HIV. Methods: PBMCs were isolated from 20 patients with HIV and chronic HCV (median CD4 386, range 167-766) and 19 patients with chronic HCV alone. ELISPOT assays were performed for IFNgamma, TNFalpha and IL-10 using HCV antigens (Ag) Core, NS3 and NS5, recall Ag tetanus and Candida, and PHA. Averaged numbers of spot- forming cells (SPC) in control wells were subtracted from Ag-stimulated wells to correct for spontaneous cytokine production. Responses were defined as greater than six mean SFC per million PBMC. Data were compared using the Fisher exact test. Results: Only one patient in each group produced IFNgamma to HCV Ag. Significantly more HCV patients than HIV/HCV patients produced IFNgamma in response to Candida (17/19 versus 9/20, p < 0.01) and tetanus (11/19 versus 3/20, p < 0.02). In the HIV/HCV group, there was no correlation between IFNgamma response to Candida and CD4 count. The TNFalpha responses in HCV versus HIV/HCV were, respectively, core (0/16 vs. 1/20), NS3 (1/16 vs. 3/20), NS5 (1/16 vs. 3/20), Candida (6/16 vs. 10/20) and tetanus (4/16 vs. 7/20) (p > 0.05 for all Ag). IL-10 responses in HCV versus HIV/HCV were core (1/19 vs. 3/20), NS3 (2/19 vs. 5/20), NS5 (2/19 vs. 5/20), Candida (5/19 vs. 2/20), and tetanus (4/19 vs. 2/10) (p > 0.05 for all Ag). Six HIV/HCV patients had IL-10 responses to one or more HCV Ag compared with two HCV patients. Conclusions: Patients with HCV are more likely to have IFNgamma responses to recall Ag but not HCV Ag, compared with HIV/HCV patients. Though not significant in this small group of patients, 30% of HIV/HCV patients had IL-10 responses to HCV Ag, compared with 10% of HCV patients. Therefore, enhanced progression of fibrosis may be due not to a loss of HCV- specific responses but rather to qualitative differences in immune function.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- CD4 Lymphocyte Count
- Disease Progression
- HIV
- HIV Infections
- HIV Seropositivity
- Hepacivirus
- Hepatitis C
- Hepatitis C Antigens
- Humans
- Interleukin-10
- T-Lymphocytes
- immunology
Other ID:
UI: 102244347
From Meeting Abstracts