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

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.

HIV–TB co‐infection: mechanisms that drive reactivation of Mycobacterium tuberculosis in HIV infection

“…Recent reports have conclusively shown that >80% of the CD4 + T-cell subset that responded to Mtb-specific CD4 T-cell epitopes, identified by a genomewide screen, displayed the CXCR3 + CCR6 + CCR4 À phenotype (Lindestam Arlehamn et al, 2013). Similarly, other reports also have separately confirmed that TB-antigen-specific CD4 + T cells are primarily confined to this unique memory subset (Acosta-Rodriguez et al, 2007;Pollock et al, 2015). Moreover, the CXCR3 + CCR6 + CCR4 À subset was significantly enhanced in latent TB-infected individuals compared to healthy controls (Arlehamn et al, 2014).…”

PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection

“…Fluorescence minus one (FMO) controls were included each time. Data on CD8, CCR7, CD45RA and CD127 are not included in this report, having been published separately but are included in the methods for accuracy [ 23 , 24 ].…”

Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy

“…3 Increased T-cell reactivity to mycobacterial purified protein derivative (PPD) has been reported in individuals without active TB, irrespective of a concomitant HIV infection as reflected by strong Th1 responses (interferon gamma (IFN-g)) and tumour necrosis factor alpha (TNF-a) production in response to CMV, while EBV-specific IFNg/TNF-a responses were generally weaker than CMV or PPD responses. 4,5 The immune reactivity to EBV and CMV among patients with active pulmonary TB has not been explored, particularly in the context of survival. Using whole blood assays and enzyme-linked immunosorbent assay (ELISA), we present here the IFN-g responses in peripheral blood of patients pulmonary TB to CMV and EBV antigens versus survival in the course of standard anti-TB therapy.…”