Two types of poor immunological responder showing distinct responses to long-term HAART

Kong, Yaxian; Tian, Yunfei; Yu, Honggang; Chong, Xuejing; Xiao, Jing; Yang, Di; Song, Chuan; Han, Junyan; Dai, Guorui; Zhang, Fujie; Zheng, Hong; Zhao, Hongxin; Zeng, Hui

doi:10.1016/j.ijid.2019.07.037

Cited by 6 publications

(7 citation statements)

References 46 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These PIRs had a higher risk of AIDS-related and non-AIDS complications, such as cardiovascular disease, bone, and renal disease, neurocognitive decline, and premature aging ( 40 – 43 ). Notably, PIRs had higher rates of morbidity and mortality than IRs ( 5 ). Thus, there is an urgent need to identify PIRs early and provide effective treatment as soon as possible.…”

Section: Discussionmentioning

confidence: 98%

“…The expression of ectonucleotidases (CD39 and CD73) on αβDNT and activated Treg cells was evaluated by flow cytometry. The gating strategy for activated Treg cells was performed as previously described ( 5 ). PBMCs were stained with directly conjugated antibodies for 30 min at 4°C in the dark.…”

Section: Methodsmentioning

confidence: 99%

“…However, part of patients (from 15% to 30%) remained insufficient in immune recovery, leading to a high risk of AIDS-related and non-AIDS complications. These patients were classified as poor immunological responders (PIRs), which had higher rates of morbidity and mortality than immunological responders (IRs) ( 2 – 5 ). Thus, it is a major clinical challenge and urgently needed to identify PIRs early and improve their immune homeostasis in time.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Wang

Zhang

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Wang

Zhang

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…45 However, our previous study indicated that thymic output and CD4 + T-cell recovery could be further improved after long-term ART. 46 Thus, a longer follow-up may be required after the ART to assess CD4 + T-cell function status. In addition, our results highlight the importance of developing novel, effective HIV treatments that can overcome the limitations of ART.…”

Section: Discussionmentioning

confidence: 99%

Altered T-Cell Subsets are Associated with Dysregulated Cytokine Secretion of CD4+ T Cells During HIV Infection

Wang¹,

Jiang²,

Song³

et al. 2021

JIR

Self Cite

View full text Add to dashboard Cite

Background: CD4 + T cells play a critical role in the regulation of immunopathogenesis in HIV infection. Previous studies have shown contradictory results of the CD4 + T-cell responses in people living with HIV (PLHIV). Methods: A cross-sectional study was performed on 40 healthy controls, 134 ART-naïve PLHIV, and 34 individuals who experienced 3-year ART with low baseline CD4 count from 4 August 2016 to 23 January 2019. We determined the frequencies of CD4 + T-cell subsets and described the cytokine secretion pattern of total and subsets of CD4 + T cells in these individuals. Results: We found that CD4 + T cells in PLHIV displayed enhanced secretion of proinflammation cytokines and polyfunctionality due to HIV disease progression (r = −0.282, P = 0.0035 for IFN-γ; r = −0.412, P = 0.0002 for TNF-α; r = −0.243, P < 0.0001 for GM-CSF; r = −0.252, P = 0.0093 for IFN-γ + TNF-α + cells). However, the altered T-cell subsets, as presented by the loss of naïve cells and expansion of memory/effector population in PLHIV, were associated with discordant results in total and subsets of CD4 + T cells. As major cytokine-producing T subsets, effector/memory CD4 subsets showed impaired cytokine production (P < 0.05). We further demonstrated that 3-year ART treatment could improve CD4 counts by increasing the pool of naïve T cells but could not restore cytokine secretion in CD4 + T-cell subsets (P < 0.05). Conclusion: These data identified the impaired capacity of cytokine secretion in CD4 + T-cell subsets due to HIV disease progression, and the altered T-cell subsets were associated with pseudo-elevation of cytokine production in total CD4 + T cells. This study collectively suggested the importance of therapies that can preserve and/or enhance the function of CD4 + T cells in strategies of HIV remission.

show abstract

“…CD4 + cell count > 350 cells/µL and HIV RNA < 200 copies/mL after cART are considered as a successful treatment in PLWHs [ 20 ]. The humoral and cellular immune responses to HBV vaccination in these satisfactory patients when they are vaccinated with 20 µg of recombinant HBV DNA vaccine at weeks 0, 4, and 24 are unknown at present.…”

Section: Introductionmentioning

confidence: 99%

Immune Responses to HBV Vaccine in People Living with HIV (PLWHs) Who Achieved Successful Treatment: A Prospective Cohort Study

Zhang

Kang

et al. 2023

Vaccines

View full text Add to dashboard Cite

Background: Understanding immune responses after HBV vaccination is important to prevent HBV infection in PLWH and to achieve successful treatment. Methods: Thirty-two PLWHs with CD4+ cell count > 350 cells/µL and HIV RNA < 200 copies/mL were vaccinated with 20 µg of HBV vaccine at weeks 0, 4, and 24 in this prospective study. We measured total HIV DNA levels, HBsAb titers and HBsAg-specific T-cell responses during follow-up time. Results: All patients achieved protective HBsAb titer after immunization. The magnitude of the IFN-r and TNF-a response to HBsAg was 22.0 (IQR: 6.5–65.0) and 106.50 (IQR: 58.5–203.0) spot-forming cells (SFC)/105 PBMC, respectively at week 0. The level of IFN-r secreted at weeks 12 and weeks 36 to 48 was comparable with that at week 0. However, IFN-r response was higher at weeks 12 than that at weeks 36 to 48 (p = 0.02). The level of TNF-a secreted at weeks 12 was higher than that at week 0 (p < 0.001). Total HIV DNA levels were 2.76 (IQR: 2.47–3.07), 2.77 (IQR: 2.50–3.09), 2.77 (IQR: 2.41–2.89) log10 copies/106 PBMCs at weeks 0, 12, 36 to 48, respectively. No correlation was observed between IFN-r and TNF-a levels and HBsAb titer as well as total HIV DNA levels after immunization. Conclusion: Humoral immunity was satisfactory, but cellular immunity and decline in HIV reservoir were not optimal after HBV vaccine immunization in these patients.

show abstract

Two types of poor immunological responder showing distinct responses to long-term HAART

Cited by 6 publications

References 46 publications

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Altered T-Cell Subsets are Associated with Dysregulated Cytokine Secretion of CD4+ T Cells During HIV Infection

Immune Responses to HBV Vaccine in People Living with HIV (PLWHs) Who Achieved Successful Treatment: A Prospective Cohort Study

Contact Info

Product

Resources

About