Reduced Type 1 and Type 2 Cytokines in Antiviral Memory T Helper Function Among Women Coinfected with HIV and HCV

Abstract

Bias in cytokine responses has been proposed as a contributing mechanism to pathogenesis in persistent HIV or hepatitis C virus (HCV) infections. We investigated whether coinfection with HCV modifies the profile of antigen-specific cytokine secretion in women persistently infected with HIV compared to women with single HIV or HCV infection. The T helper response to HIV, HCV and cytomegalovirus (CMV) as a positive viral control was dominated by type 1 cytokines ( interleukin-[IL] 2, interferon-[IFN] γ and tumor necrosis factor-[TNF] α), with IFN-γ as the most abundantly secreted. IL-4, IL-5 and IL-10 were low in healthy controls and patients. Robust CMV-specific responses contrasted with curtailed HCV-specific responses in HCV-infected women. The overall anti-viral profile was dominated by Th1 cytokines even in coinfected women but both type 1 and type 2 responses were reduced in HIV-infected women and more extensively in women with HCV/HIV coinfection.

A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy

“…The levels of IL‐4 and IFN‐γ mRNA correlated with each other and with IL‐5 and IL‐4δ2 mRNA levels after anti‐CD3 stimulation, where IL‐5 mRNA levels were the best predictor of IFN‐γ mRNA levels after stimulation with anti‐CD3 ( P = 0·006). This is consistent with a positive correlation between the levels of T1 cytokines [IL‐2 plus IFN‐γ and tumour necrosis factor‐α (TNF‐α)] and T2 cytokines (IL‐4, IL‐5 and IL‐10) described in HIV‐ and HCV‐infected women, 30 and contrasts with active tuberculosis and asthma where there is excess IL‐4 mRNA relative to IL‐4δ2 or IFN‐γ 14,18 , 31 . Excess IL‐4δ2 has been linked with inhibition of IL‐4‐mediated B‐cell activation, 32 which provides an explanation for the association between a high IL‐4/IL‐4δ2 ratio and elevated IgE in asthmatics 31 .…”

Evaluating the Impact of Hepatitis C Virus (HCV) on Highly Active Antiretroviral Therapy–Mediated Immune Responses in HCV/HIV‐Coinfected Women: Role of HCV on Expression of Primed/Memory T Cells

“…A recent report indicated that T helper responses are impaired in coinfected patients to a greater extent than monoinfected patients, as measured by effector function responses [37]. Therefore, HCV infection may lead to additional functional impairments without altering the number of such cells.…”

Defective response to Toll‐like receptor 3 and 4 ligands by activated monocytes in chronic hepatitis C virus infection

“…In human immunodeficiency virus (HIV)‐infected individuals, HCV co‐infection appears linked to increased morbidity and mortality [5–7]. We and others have previously reported more extensive T helper cell dysfunction in patients with HIV / HCV co‐infection compared with individuals with either HIV or HCV mono‐infection [8,9]. Although reduced CD4 cell counts in HIV‐infected individuals have a significant impact on immune function, emerging investigations suggest that additional levels of dysfunction linked to HCV may also exist.…”