Related Experiment Video
Updated: Mar 9, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV
Marie-Quitterie Picat1,2,3,4,5, Isabelle Pellegrin6, Juliette Bitard6
1Centre INSERM U1219 Bordeaux Population Health, Bordeaux, France.
Insights
Cytomegalovirus (CMV) directly impacts chronic immune activation (CIA) in treated HIV patients. Autoimmunity indirectly affects CIA through alpha-interferon, warranting further study in HIV management.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Chronic immune activation (CIA) persists in successfully treated HIV-infected patients.
- Understanding the interplay between viral infections, autoimmunity, and immune activation is crucial for managing long-term HIV complications.
Purpose of the Study:
- To investigate the relationships between cytomegalovirus (CMV)-induced responses, autoimmune-induced responses, microbial translocation, and CIA in treated HIV patients.
- To explore the mediating role of alpha-interferon (IFN-α) in these complex interactions.
Main Methods:
- A cross-sectional study within the ANRS CO3 Aquitaine Cohort of HIV-1-infected patients on sustained antiretroviral therapy.
- Structural equation modeling (SEM) was used to analyze data, including CMV responses (Quantiferon, ELISPOT), autoimmune markers, and IFN-α-stimulated genes.
- Chronic immune activation (CIA) was defined by HLA-DR+/CD38+ expression on CD8+ T-cells.
Main Results:
- CMV-induced response directly impacted CIA (βstd = 0.56, p=0.0004).
- Autoimmune response indirectly influenced CIA via the alpha-interferon pathway (autoimmunity to IFN-α: βstd = 0.36, p=0.0401; IFN-α to CIA: βstd = 0.39, p=0.0044).
- Microbial translocation was not associated with CIA. The IFN-α latent variable significantly affected CIA across analyses.
Conclusions:
- The direct effect of CMV on CIA and the involvement of alpha-interferon in CIA are confirmed.
- The indirect role of autoimmunity in CIA through the alpha-interferon pathway requires further investigation.
- These findings highlight potential therapeutic targets for managing chronic immune activation in HIV-infected individuals.
Objectives:
To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes.
Design:
Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France.
Methods:
Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM).
Results:
The main analysis was performed in 57 HLA-A*0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A*0201 positive patients and in the overall population revealed a significant effect of IFN-α latent variable on CIA.
Conclusion:
The role of cytomegalovirus-induced response on CIA was confirmed as well as the involvement of alpha-interferon on CIA. The indirect effect of auto-immunity response on CIA revealed through the alpha-interferon pathway requires further investigation to confirm the potential role of auto-immunity for CIA in HIV-infected patients.
