Plasma CD16<sup>+</sup>Extracellular Vesicles Associate with Carotid Artery Intima-Media Thickness in HIV<sup>+</sup>Adults on Combination Antiretroviral Therapy

Menezes, Erika G Marques de; Deng, Xutao; Liu, Jocelyn; Bowler, Scott; Shikuma, Cecilia; Stone, Mars; Hunt, Peter W.; Ndhlovu, Lishomwa C.; Norris, Philip J.

doi:10.1128/mbio.03005-21

Cited by 8 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We mimicked the conditions in the bloodstream in vivo as closely as possible, by studying the autologous blood EVs present in plasma directly, without ultracentrifugation. The results obtained with this direct phenotyping method were similar to published results, particularly for the phenotyping of EVs in HDs ( 2 , 3 , 14 ).. This direct plasma EV phenotyping also revealed heterogeneity in the numbers and size distribution of EVs ( Supplemental Table 1 ).…”

Section: Discussionsupporting

confidence: 86%

See 1 more Smart Citation

Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation

et al. 2022

View full text Add to dashboard Cite

Extracellular vesicles (EVs), which are generated by cell membrane budding in diverse cells, are present in variable numbers in the blood. An immunoregulatory role has been demonstrated principally for heterologous EVs, but the function of the EVs present naturally in blood remains unknown. We hypothesize that these autologous EVs might also modulate the phenotype and function of immune system cells, especially CD4+ T lymphocytes (TLs), as previously described for heterologous EVs. Several membranes and soluble immunoregulatory molecules were studied after the treatment of CD4+ TLs with autologous EVs. No direct activation was detected with autologous EVs, contrasting with the findings for heterologous EVs. However, following treatment with autologous EVs, a soluble form of CD27 (sCD27) was detected. sCD27 is strongly associated with lymphoproliferation. Autologous EVs have been shown to increase TL proliferation only after T-cell receptor (TcR) engagement due to polyclonal or specific-antigen stimulation. Our results therefore suggest that the EVs present in the blood have an immunomodulatory role different from that of heterologous EVs. These findings should be taken into account in future studies, particularly those focusing on infectious diseases, autotransfusion or doping practices.

show abstract

Section: Discussionsupporting

confidence: 86%

“…However, sCD27 may also be provided by CD27 + EVs during culture. Indeed, the presence of CD27 + EVs has recently been reported in the plasma of HIV-infected patients ( 14 ). We purified CD27 + EVs by flow cytometry to test this hypothesis.…”

Section: Discussionmentioning

confidence: 95%

Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…High plasma sCD27 concentrations are associated with poor patient survival ( 9 ). A vesicular form of CD27 has been found in plasma from healthy blood donors (HDs) ( 12 , 13 ). Two types of extracellular vesicle have been identified: exosomes (small vesicles, 40-100 nm in diameter, derived from intracellular membrane compartments), and larger extracellular vesicles (200-900 nm in diameter, generated by the budding of the cell membrane) known as microparticles (MPs) or ectosomes ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

CD27+ microparticle interactions and immunoregulation of CD4+ T lymphocytes

et al. 2023

View full text Add to dashboard Cite

IntroductionAplasia and hematological malignancies are treated with platelet transfusions, which can have major immunomodulatory effects. Platelet concentrates (PCs) contain many immunomodulatory elements, including the platelets themselves, residual leukocytes, extracellular vesicles, such as microparticles (MPs), cytokines and other soluble elements. Two of these components, MPs and a soluble form of CD27 (sCD27), have been shown to play a particularly important role in immune system modulation. The loss of CD27 expression is an irreversible marker of terminal effector CD3+ T-lymphocyte (TL) differentiation, and the CD27+ MPs present in PCs may maintain CD27 expression on the surface of TLs, and, thus, the activation of these cells.MethodsIn this study, we phenotyped the CD27-expressing MPs present in PCs by microscale flow cytometry and investigated the interaction of these particles with CD4+ TLs. We cocultured MPs and PBMCs and determined the origin of the CD27 expressed on the surface of CD4+ TLs with the aid of two fluorochromes (BV510 for CD27 originating from MPs and BV786 for cellular CD27).ResultsWe showed that the binding of CD27- expressing MPs involved the CD70 molecule, which was also present on these MPs. Finally, the maintenance of CD27 expression on the surface of TLs by sorted CD27+ MPs led to activation levels lower than those observed with other types of MPs.DiscussionThese results for CD27-expressing MPs and their CD70-mediated targeting open up new possibilities for immunotherapy based on the use of MPs to maintain a phenotype or to target immune cells, for example. Moreover, decreasing the levels of CD27-expressing MPs in transfused platelets might also increase the chances of success for anti-CD27 monoclonal immunotherapy.

show abstract

“…A 0.22 µm-filtered PBS control was recorded to estimate the background signal. EV gates were established 100 nm (Invitrogen) to 1000 nm beads (Megamix: 160, 200, 240 and 500 nm; Spherotech 1000 nm) ( 26 , 41 , 42 ). Representative flow cytometry plots are shown in Figure 1C .…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we recently showed that plasma-EVs expressing monocyte markers are associated with carotid artery intima-media thickness in HIV-infected individuals on virologically suppressive ART. We further showed that the EV fraction from HIV+ adults on stable ART induced endothelial cell death via necrosis of human umbilical vein endothelial cells ( 26 ). These properties make EVs potential candidates as targets of immunotherapies and putative biomarkers for diseases ( 17 , 27 – 30 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating brain-derived extracellular vesicles expressing neuroinflammatory markers are associated with HIV-related neurocognitive impairment

et al. 2022

Self Cite

View full text Add to dashboard Cite

BackgroundNeurocognitive impairment remains prevalent in people with HIV (PWH) despite long term virological suppression by antiretroviral therapy (ART) regimens. Systemic and neuro-inflammatory processes are suggested to contribute to the complex pathology leading to cognitive impairment in this population, yet the underlying mechanisms remain unresolved. Extracellular vesicles (EVs) play a central role in intracellular communication and have emerged as key modulators of immunological and inflammatory responses. In this report, we examined the impact of EVs in PWH experiencing cognitive deficits to determine their relevance in HIV associated neuropathology.MethodsEV phenotypes were measured in plasma samples from 108 PWH with either cognitive impairment (CI, n=92) or normal cognition (NC, n=16) by flow cytometry. Matched cerebrospinal fluid (CSF)-derived EVs were similarly profiled from a subgroup of 84 individuals who underwent a lumbar puncture. Peripheral blood mononuclear cells were assayed by flow cytometry to measure monocyte frequencies in a subset of 32 individuals.ResultsPlasma-EVs expressing CD14, CD16, CD192, C195, and GFAP were significantly higher in HIV-infected individuals with cognitive impairment compared to individuals with normal cognition. Increased CSF-EVs expressing GFAP and CD200 were found in the cognitive impairment group compared to the normal cognition group. Frequencies of patrolling monocytes correlated with plasma-EVs expressing CD14, CD66b, MCSF, MAP2, and GFAP. Frequencies of CD195 expression on monocytes correlated positively with plasma-EVs expressing CD41a, CD62P, and CD63. Expression of CD163 on monocytes correlated positively with CSF-EVs expressing GFAP and CD200. Finally, the expression of CD192 on total monocytes correlated with CSF-EVs expressing CD200, CD62P, and CD63.ConclusionsEVs expressing monocyte activation and neuronal markers associated with HIV associated cognitive impairment, suggesting that distinct EV subsets may serve as novel biomarkers of neuronal injury in HIV infection. Further circulating platelet EV levels were linked to monocyte activation indicating a potential novel interaction in the pathogenesis of HIV-related cognitive impairment.

show abstract

Plasma CD16⁺Extracellular Vesicles Associate with Carotid Artery Intima-Media Thickness in HIV⁺Adults on Combination Antiretroviral Therapy

Cited by 8 publications

References 53 publications

Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation

Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation

CD27+ microparticle interactions and immunoregulation of CD4+ T lymphocytes

Circulating brain-derived extracellular vesicles expressing neuroinflammatory markers are associated with HIV-related neurocognitive impairment

Contact Info

Product

Resources

About

Plasma CD16+Extracellular Vesicles Associate with Carotid Artery Intima-Media Thickness in HIV+Adults on Combination Antiretroviral Therapy

Cited by 8 publications

References 53 publications

Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation

Autologous blood extracellular vesicles and specific CD4+ T-cell co-activation

CD27+ microparticle interactions and immunoregulation of CD4+ T lymphocytes

Circulating brain-derived extracellular vesicles expressing neuroinflammatory markers are associated with HIV-related neurocognitive impairment

Contact Info

Product

Resources

About

Plasma CD16⁺Extracellular Vesicles Associate with Carotid Artery Intima-Media Thickness in HIV⁺Adults on Combination Antiretroviral Therapy