Concerted effect of lymphopenia, viraemia and T-cell activation on Fas expression of peripheral B cells in HIV-1-infected patients

Réthi, Bence; Sammicheli, Stefano; Amu, Sylvie; Pensieroso, Simone; Hejdeman, Bo; Schepis, Danika; Thắng, Phạm Hồng; Chiodi, Francesca

doi:10.1097/qad.0b013e32835b8c5e

Cited by 22 publications

(28 citation statements)

References 18 publications

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“…Many of the genes with increased expression, including granzyme B (GZMB), 29 a calcium binding protein (S100A6), 30 a gap junction protein (GJA1), 31 and a cyclin-dependent kinase inhibitor (CDKN2A), 32 have been reported to have a role in cell death and/or apoptosis. Several genes showing decreased expression, including the inhibitory receptor of peripheral mononuclear cells (LAIR1), 33 a conserved cysteine-rich protein (PLAC8), 34 an apoptosis-associated speck-like protein (PYCARD), 35 and a receptor tyrosine kinase (ERBB3), 36 have also been reported to have a role in cell death. CARD11, a caspase recruitment domain-containing protein, has decreased expression and been reported to interact with the proapoptotic BCL10 protein.…”

Section: Resultsmentioning

confidence: 99%

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

et al. 2015

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We developed a model system to investigate apoptotic resistance in T cells using osmotic stress (OS) to drive selection of deathresistant cells. Exposure of S49 (Neo) T cells to multiple rounds of OS followed by recovery of surviving cells resulted in the selection of a population of T cells (S49 ) that failed to die in response to a variety of intrinsic apoptotic stimuli including acute OS, but remained sensitive to extrinsic apoptotic initiators. Genome-wide microarray analysis comparing the S49 (OS 4-25) with the parent S49 (Neo) cells revealed over 8500 differentially regulated genes, with almost 90% of those identified being repressed. Surprisingly, our data revealed that apoptotic resistance is not associated with expected changes in pro-or antiapoptotic Bcl-2 family member genes. Rather, these cells lack several characteristics associated with the initial signaling or activation of the intrinsic apoptosis pathway, including failure to increase mitochondrial-derived reactive oxygen species, failure to increase intracellular calcium, failure to deplete glutathione, failure to release cytochrome c from the mitochondria, along with a lack of induced caspase activity. The S49 (OS 4-25) cells exhibit metabolic characteristics indicative of the Warburg effect, and, despite numerous changes in mitochondria gene expression, the mitochondria have a normal metabolic capacity. Interestingly, the S49 (OS 4-25) cells have developed a complete dependence on glucose for survival, and glucose withdrawal results in cell death with many of the essential characteristics of apoptosis. Furthermore, we show that other dietary sugars such as galactose support the viability of the S49 (OS 4-25) cells in the absence of glucose; however, this carbon source sensitizes these cells to die. Our findings suggest that carbon substrate reprogramming for energy production in the S49 (OS 4-25) cells results in stimulusspecific recognition defects in the activation of intrinsic apoptotic pathways.

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Section: Resultsmentioning

confidence: 99%

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

et al. 2015

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“…As the number of naive B cells also increased significantly in the patients treated with antiretrovirals in relation to healthy controls, the lower frequency of transitional, activated memory, and TLM B cells may only reflect distribution dynamics within the B-cell compartment in the treated patients. As an alternative explanation, it should be considered that activated memory and TLM B cells are activated cells with a pro-apoptotic phenotype [26] and may progressively be depleted over time during antiretroviral therapy.…”

Section: Discussionmentioning

confidence: 99%

B-cell subset alterations and correlated factors in HIV-1 infection

Pensieroso

Galli

Nozza

et al. 2013

Aids

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“…Our group has recently shown that PD-1 expression on B cells was substantially elevated only on the resting memory B-cell subset of HIV-1 viremic individuals. This observation suggests that PD-1 might contribute to the reduced maintenance of this subset of B cells [42]. A previous study conducted in simian immunodeficiency virus (SIV)-infected macaques [40] showed that early depletion of PD-1 expressing activated memory B cells is associated with a more rapid disease progression.…”

Section: Redistribution Of Classic and Rare Populations Of Memory B Cmentioning

confidence: 97%

“…They may result from increased susceptibility to apoptosis due to altered expression of receptors important for survival and cell death [7,[40][41][42], altered homing to and presence within the lymphoid tissue as a consequence of altered expression of molecules pivotal for homing of B cells, for example, CXCR5/CXCL13 [43] and/or increased differentiation of B cells toward plasma cells [10]. Studies on population dynamics of the B-cell compartment may contribute to new and important explanations for the changes in proportions of B-cell subpopulations during HIV-1 infection.…”

Section: Redistribution Of Classic and Rare Populations Of Memory B Cmentioning

confidence: 99%

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Impairment of B-cell functions during HIV-1 infection

Amu

Ruffin

Réthi

et al. 2013

Aids

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A variety of B-cell dysfunctions are manifested during HIV-1 infection, as reported early during the HIV-1 epidemic. It is not unusual that the pathogenic mechanisms presented to elucidate impairment of B-cell responses during HIV-1 infection focus on the impact of reduced T-cell numbers and functions, and lack of germinal center formation in lymphoid tissues. To our understanding, however, perturbation of B-cell phenotype and function during HIV-1 infection may begin at several different B-cell developmental stages. These impairments can be mediated by intrinsic B-cell defects as well as by the lack of proper T-cell help. In this review, we will highlight some of the pathways and molecular interactions leading to B-cell impairment prior to germinal center formation and B-cell activation mediated through the B-cell receptor in response to HIV-1 antigens. Recent studies indicate a regulatory role for B cells on T-cell biology and immune responses. We will discuss some of these novel findings and how these regulatory mechanisms could potentially be affected by the intrinsic defects of B cells taking place during HIV-1 infection.

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Concerted effect of lymphopenia, viraemia and T-cell activation on Fas expression of peripheral B cells in HIV-1-infected patients

Abstract: Fas is regulated by the concerted action of viraemia, lymphopenia and T-cell activation during HIV-1 infection, and Fas expression is altered on all peripheral B-cell subsets. Resting memory B-cell homeostasis shows the highest sensitivity to HIV-1-induced perturbations.

Cited by 22 publications

References 18 publications

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

B-cell subset alterations and correlated factors in HIV-1 infection

Impairment of B-cell functions during HIV-1 infection

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