Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination

Luo, Zhenwu; Zhang, Lumin; Martin, Lisa; Wan, Zhuang; Warth, Stephanie; Kilby, Andrew; Gao, Yong; Bhargava, Pallavi; Li, Zhen; Wu, Hao; Meissner, Eric G.; Li, Zihai; Kilby, J Michael; Liao, Guoyang; Jiang, Wei

doi:10.1016/j.vaccine.2015.12.038

Cited by 13 publications

(19 citation statements)

References 48 publications

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“…These results differ from results reported by others (15,36) and might be explained by a longer duration of ART treatment (more than 10 y on with an average of 4-21 y) in our cohort of l-ART patients. However, according to our results, a partial restoration of a normal homeostasis of B cell populations with a decrease of AM and TLM B cells has been reported in chronically ART-treated patients (37,38). Altogether, our results underscore the interest to study changes in B cell populations in various compartments, revealing in this study that if e-ART may limit the major B cell subset alterations in the gut, they are only partially restored even in the long term.…”

Section: Discussionsupporting

confidence: 79%

Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1–Infected Individuals

Planchais

Hocqueloux

Ibáñez

et al. 2018

The Journal of Immunology

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HIV-1 infection is associated with B cell dysregulation and dysfunction. In HIV-1-infected patients, we previously reported preservation of intestinal lymphoid structures and dendritic cell maturation pathways after early combination antiretroviral therapy (e-ART), started during the acute phase of the infection, compared with late combination antiretroviral therapy started during the chronic phase. In this study, we investigated whether the timing of combination antiretroviral therapy initiation was associated with the development of the HIV-1-specific humoral response in the gut. The results showed that e-ART was associated with higher frequencies of functional resting memory B cells in the gut. These frequencies correlated strongly with those of follicular Th cells in the gut. Importantly, frequencies of HIV-1 Env gp140-reactive B cells were higher in patients given e-ART, in whom gp140-reactive IgG production by mucosal B cells increased after stimulation. Moreover, IL-21 release by PBMCs stimulated with HIV-1 peptide pools was greater with e-ART than with late combination antiretroviral therapy. Thus, early treatment initiation helps to maintain HIV-1-reactive memory B cells in the gut as well as follicular Th cells, whose role is crucial in the development of potent affinity-matured and broadly neutralizing Abs.

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Section: Discussionsupporting

confidence: 79%

Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1–Infected Individuals

Planchais

Hocqueloux

Ibáñez

et al. 2018

The Journal of Immunology

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“…All HIV + patients had been on ART treatment and had undetectable plasma HIV-1 RNA (,50 copies/ml) for at least 2 yr. The clinical characteristics of patients were shown in our previous study [13]. This study was approved by the Institutional Review Board from the Medical University of South Carolina.…”

Section: Study Subjectsmentioning

confidence: 99%

The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV-infected patients under antiretroviral therapy

Luo

Zhou

Ogunrinde

et al. 2017

Journal of Leukocyte Biology

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Although effective antiretroviral therapy (ART) suppresses HIV viral replication, prevents AIDS-related complications, and prolongs life, a proportion of patients fails to restore the patients' CD4 T cell number to the level of healthy individuals. Increased mortality and morbidity have been observed in these patients. In the current study, we have investigated the role of auto-IgGs in CD4 T cell apoptosis and recovery in a cross-sectional study. All HIV subjects were on viral-suppressive ART treatment with a different degree of CD4 T cell reconstitution. Total auto-IgG binding on CD4 T cell surfaces and its associated apoptosis and CD4 T cell recovery were analyzed by flow cytometry ex vivo. Total IgGs from plasma were tested for their binding capacities to CD4 T cell surfaces and their mediation to CD4 T cell death through NK cell cytotoxicity in vitro. HIV subjects had increased surface binding of auto-IgGs on CD4 T cells compared with healthy controls, and IgG binding was associated with elevated CD4 T cell apoptosis in HIV subjects but not in healthy controls. Plasma IgGs from HIV subjects bound to CD4 T cells and induced cell apoptosis through NK cytotoxicity in vitro. Soluble CD4 (sCD4) preincubation prevented NK cell-mediated CD4 T cell death. Our results suggest that plasma autoantibodies may play a role in some HIV patients with poor CD4 T cell recovery under viral-suppressive ART.

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“…This study was approved by the Medical University of South Carolina IRB (Pro00020606), and all participants provided written informed consent. We previously reported that anti-H1N1 neutralizing antibody response was the predominant viral strain [14]. Therefore vaccine responders were defined as a four-fold increase in neutralization from baseline titers on D14, and non-responders were defined as less than a four-fold increase in neutralization from baseline titers against H1N1 virus [15].…”

Section: Methodsmentioning

confidence: 99%

“…The detailed method was descripted in our previous study [14]. Briefly, plasma samples were serial diluted and heat-inactivated.…”

Section: Methodsmentioning

confidence: 99%

The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals

Powell

Luo

Martin

et al. 2017

Vaccine

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Background Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART). Methods 16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7–10 (D7) and 14–21 (D14) following the 2013–2014 seasonal influenza vaccine administrations. Subjects were classified as responders if neutralizing titers against H1N1 virus increased ≥ 4-fold at D14 compared to D0. A serial analysis of B and CD4+ T cell frequencies and activation was performed on D0 and D7 by flow cytometry. Results 9 of 26 (34.6%) HIV-infected individuals and 7 of 16 (43.8%) healthy controls were classified as responders to influenza vaccines. Total B cell apoptosis (annexin V) was increased on D7 post-vaccination in non-responders but not in responders among both controls and HIV+ subjects. Surface CD80 expression on memory B cells and intracellular CD40L expression on memory CD4+ T cells were induced on D7 in responders of controls but not in non-responders. The CD80 and CD40L induction was not demonstrable in HIV-infected subjects regardless of responders and non-responders. Memory CD4+ T cell cycling tended to increase on D7 in the four study groups but did not achieve significance. All the other parameters were indistinguishable between responders and non-responders, regardless of HIV-infection status. Conclusion The perturbation of activation and apoptotic induction on B cells or CD4+ T cells after seasonal influenza vaccination in non-responders and HIV-infected subjects may help understand the mechanism of impaired vaccine responsiveness.

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Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination

Cited by 13 publications

References 48 publications

Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1–Infected Individuals

Early Antiretroviral Therapy Preserves Functional Follicular Helper T and HIV-Specific B Cells in the Gut Mucosa of HIV-1–Infected Individuals

The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV-infected patients under antiretroviral therapy

The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals

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