Pathophysiology of CD4+ T-Cell Depletion in HIV-1 and HIV-2 Infections

Vijayan, Kamalakannan; Karthigeyan, Krithika Priyadarshini; Tripathi, S; Hanna, Luke Elizabeth

doi:10.3389/fimmu.2017.00580

Cited by 200 publications

(160 citation statements)

References 81 publications

(98 reference statements)

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“…Association neither positive nor negative was found between frailty and naïve or memory subsets. One of the strongest correlates for CD4 + T cell decline in HIV-1 infection is the increased frequency of CD4 M T cells and a corresponding deficit of CD4 N T cells [38]. The Frail group exhibited a decreased frequency of CD4 M cells (27.63 vs. 32.88) and an increase in CD4 N (25.11 vs. 20.05) compared to the non-frail group, but these results were not statistically significant (Fig 1a and 1b).…”

Section: Levels Of Cd4 and Cd8 T Cells In Frail Individualsmentioning

confidence: 99%

Frailty, markers of immune activation and oxidative stress in HIV infected elderly

et al. 2020

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People living with HIV-1 experience an accelerated aging due to the persistent and chronic activation of the immune system. This phenomenon conduces to immune exhaustion and precipitate immunosenescence. In general, frailty is defined as a syndrome of physiological degeneration in the elderly. Circulating naïve and memory T cells were studied by flow cytometry in non-frail and frail HIV-1-infected groups. Thymopoiesis, cell activation, senescence and cell proliferation were analyzed by CD31, HLA-DR/CD38, CD28/CD57 and Ki-67 expression, respectively. Plasma levels of sCD14 and MDA were measured by ELISA. Frail infected individuals showed a reduced number of memory T cells, both CD4 + and CD8 + populations. Activated CD3 + CD4 + HLA-DR + T cells were lower in frail individuals, and directly correlated with CD3 + CD8 + HLA-DR + and CD8 M cells. Senescent CD8 + CD28 − CD57 + cells were reduced in frail HIV-1 infected individuals and inversely correlated with CD8 RTE , CD8 N and CD3 + CD4 + HLA-DR +. Higher plasma levels of sCD14 and MDA were found in HIV-1 infected frail individuals. Our data show association among frailty, markers of immune activation and oxidative stress. Understanding the immune mechanisms underlying frailty status in HIV-1 population is of high relevance not only for the prediction of continuing longevity but also for the identification of potential strategies for the elderly.

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Section: Levels Of Cd4 and Cd8 T Cells In Frail Individualsmentioning

confidence: 99%

Frailty, markers of immune activation and oxidative stress in HIV infected elderly

et al. 2020

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“…Human immunodeficiency virus damages the immune system because it targets CD4 + Tlymphocyte cells. As an infected CD4 + cell multiplies, fewer HIV-free working CD4 + cells become available, eventually decreasing the concentration of these cells in the blood (CD4 + count) (6). Consequently, patients become susceptible to a wide range of opportunistic infections, especially if they are not receiving cART.…”

Section: Introductionmentioning

confidence: 99%

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa

Lentoor

2020

Front. Neurol.

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Despite the undisputed benefits of combination antiretroviral therapy (cART), perinatally acquired human immunodeficiency virus (PHIV) children on treatment often present with a spectrum of neurological deficits known as HIV-associated neurocognitive impairment. Even higher CD4 cell count does not seem to prevent the development of neurocognitive impairment in children with PHIV. While CD4 cell count has shown to have the greatest prognostic value, its association with neurocognitive abilities remains to be clarified. This study aimed at determining the correlation between plasma CD4 + lymphocyte and neurocognitive function in children with PHIV on cART. In total, 152 purposively recruited hospital-based sample of children with PHIV on cART, aged 3 years to 7 years 6 months (mean age, 63.13 months), underwent neurocognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Immunological status of each child was based on the plasma CD4 + lymphocyte levels. The mean CD4 + lymphocyte cell count at the time of neurocognitive assessment was 1,259.85 cells/mm 3 (mean range, 139-2,717 cells/mm 3), with significant age difference on CD4 + lymphocyte count levels [F (2,149) = 13.58, p = 0.000]. CD4 + lymphocyte counts was significantly correlated with subdomains of neurocognitive function scores of task that measures working memory, processing speed, and perceptual reasoning. Global cognitive ability (Full Scale Intellectual Quotient) had no significant association with immunological status of the children. The findings support an association between immunological status of PHIV infection and executive function task. These neurocognitive faculties are critical for learning, school readiness and success in early childhood, and ultimately treatment adherence in adolescence. The need for early identification of neurodevelopment deficits in children, even when on cART, is crucial because early psychosocial and neurorehabilitative interventions can lead to better outcome for children with PHIV.

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“…It has been previously reported that the main difference in lymphoid phenotypes observed in HIV-infected patients is a reduction by 40% in the CD4+ T helper population and a 45% increase in the CD8+ cytotoxic T-cell population [10]. However, despite decades of experimental research, the complete mechanism of CD4+ T depletion in HIV infection still remains to be explained [11].…”

Section: Discussionmentioning

confidence: 99%

“…We are not able to con rm these data in our patients because they have not been evaluated using antibodies directed against the Treg cell population or their subgroups, namely the naïve-resting cells (CD45RA+) and the memory-activated cells (CD45RA−). In both virus infections, the exact reason of the reduction in the lymphocyte numbers in the blood is not clearly de ned yet and many hypotheses have been proposed [11,16]. In particular, it is not clear whether the reduction in the serum levels of T cells is due to an imbalance between production of T-cells and increased apoptosis of CD4+ T cells by viral attack the so-called of "accelerated destruction" hypothesis.…”

Section: Discussionmentioning

confidence: 99%

AIDS and COVID-19 are two diseases separated by a common lymphocytopenia

Sciacchitano

Giovagnoli

Amodeo

et al. 2020

Preprint

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HIV and SARS-CoV-2 are responsible for two of the most dangerous and life-threatening infectious diseases of our times. To better analyze the difference in the immunological response elicited by the two infections, we compare the alterations in the lymphocyte subpopulations, measured by flow cytometry analysis (FCA) in both AIDS and COVID-19 patients, referred to our University Hospital. A total of 184 HIV infected patients were retrospectively examined and the results of FCA collected and compared to those obtained in 110 SARS-CoV-2 infected patients, examined during the actual outbreak. We observe a comparable reduction in B cells in both diseases and a more severe reduction in the total amount of T cells in COVID-19 as compared to AIDS patients. The analysis of the T cells subpopulations indicates that there is a comparable reduction in the CD4+ cells count. Conversely, a remarkable difference between them is observed in the CD8+ counts. In AIDS patients the CD8+ cells are slightly higher than normal, while in COVID-19 patients the CD8+ cell count is markedly reduced. As a result, the CD4+/CD8+ ratios, is very low in AIDS and higher than normal in COVID-19 patients. The NK cells are reduced in both diseases, but SARS-CoV-2 infection causes a more severe reduction compared to HIV infection. In conclusion, both HIV and SARS-CoV-2 viruses induce major changes in the lymphocytes count, with remarkable similarities and differences between them. The total absolute numbers of T cells and, in particular of the CD8+ subpopulation, are lower in COVID-19 patients compared to AIDS ones, while the CD4+ are reduced in both at similar levels. These results indicate that the host immune system reacts differently to the two infection, but they are responsible of a comparable dropping effect on the serum levels of CD4+ T cell population. The meaning of the similarities and of the differences in terms of T cells activation and serum depletion are discussed. The knowledge on how the immune system reacts to these two infections will be useful to better define their mechanism of action and to design specific preventive and therapeutic approaches.

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Pathophysiology of CD4+ T-Cell Depletion in HIV-1 and HIV-2 Infections

Cited by 200 publications

References 81 publications

Frailty, markers of immune activation and oxidative stress in HIV infected elderly

Frailty, markers of immune activation and oxidative stress in HIV infected elderly

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa

AIDS and COVID-19 are two diseases separated by a common lymphocytopenia

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