Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection.

Katrina M Pollock,Onn M Kon,Robert D Sampson,Lisa Grass,Graham S Cooke,Ajit Lalvani,Damien J Montamat-Sicotte,Graham P Taylor,Moses S Kapembwa

doi:10.1002/iid3.50

Abstract

HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection.

Highlights

Mycobacterium tuberculosis (MTB) is a common cause of HIV-related opportunistic infection (OI) in endemic [1] and non-endemic areas [2]
CD4þ cells secreting IFN-g and TNF-a were enriched in the TEM subset for CMV, Epstein-Barr virus (EBV) and C. albicans responses but not for purified protein derivative (PPD), which were enriched in the TCM subset (Fig. 3C)
HIV co-infection was associated with an increased frequency of CMV-specific IFN-g-only and TNF-a-only CD4þ cells compared with PPD

Summary

Introduction

Mycobacterium tuberculosis (MTB) is a common cause of HIV-related opportunistic infection (OI) in endemic [1] and non-endemic areas [2]. Active antiretroviral therapy (HAART) significantly reduces disease caused by C. albicans, EBV and CMV but may be less effective in protecting against an active TB infection. HAART significantly reduced TB incidence in one study, cases still occurred in those who received HIV therapy [11]. Similar results in other cohorts suggest that whilst incidence is reduced, MTBspecific immunity may not completely regenerate with HAART and TB incidence is not restored to background levels [12]. These observations of the timing of different

Methods

Results

Conclusion