T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya : T cell anergy and activation in measles revaccination of HIV-infected children

Systemic chronic immune activation is considered today as the driving force of CD4(+) T-cell depletion and acquired immunodeficiency syndrome (AIDS). A residual chronic immune activation persists even in HIV-infected patients in which viral replication is successfully inhibited by anti-retroviral therapy, with the extent of this residual immune activation being associated with CD4(+) T-cell loss. Unfortunately, the causal link between chronic immune activation and CD4(+) T-cell loss has not been formally established. This article provides first a brief historical overview on how the perception of the causative role of immune activation has changed over the years and lists the different kinds of immune activation characteristic of human immunodeficiency virus (HIV) infection. The mechanisms proposed to explain the chronic immune activation are multiple and are enumerated here, as well as the mechanisms proposed on how chronic immune activation could lead to AIDS. In addition, we summarize the lessons learned from natural hosts that know how to 'show AIDS the door', and discuss how these studies informed the design of novel immune modulatory interventions that are currently being tested. Finally, we review the current approaches aimed at targeting chronic immune activation and evoke future perspectives. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level.

Background Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. Results Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. Conclusion T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.