Increased frequency of CD25dimCD4+ T-cells in HIV-2 infection, a naturally occurring attenuated form of HIV-1

Foxall, Russell B.; Soares, Rui; Albuquerque, Adriana S.; Cortesão, Catarina S.; Victorino, Rui M. M.; Sousa, Ana E.

doi:10.1016/j.clim.2008.01.008

Cited by 5 publications

(3 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both HIV-1 and HIV-2 infections are associated with a persistent generalized immune-activation, which is considered a main determinant of the immunodeficiency and that inversely correlates with CD4 T cell counts [22],[24],[49]. We assessed the relationship between pDC levels and expression of activation markers on T cells.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously shown that generalized immune activation is likely to be a main determinant of HIV-2 disease progression [22],[24], as has been demonstrated in HIV-1 infection [22],[24],[50],[58]. Persistent HIV-2 infection is thought to induce a chronic stimulation of the immune system leading to a progressive T cell impairment and CD4 depletion, though at much slower rates than in HIV-1 infection [22],[24],[49]. The generalized pro-inflammatory state is likely to contribute to pDC depletion both by altered cell traffic and apoptosis susceptibility, as well as through the impairment of the ability of DC precursors to differentiate.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

et al. 2009

Self Cite

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-α production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of “attenuated” HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-α production does occur.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cytokine production was assessed at single-cell level after 4 h PBMC culture with PMA/ionomycin in the presence of brefeldin A, as described [16], with mAb against IFN-γ (clone 4S.B3), IL-2 (clone MQ1-17H12), and IL-4 (clone MP4-25D2) from BD Biosciences; IL-10 (clone JES3-9D7); and IL-17 (clone eBio64DEC17) from eBiosciences.…”

Section: Methodsmentioning

confidence: 99%

Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation

et al. 2012

Self Cite

View full text Add to dashboard Cite

Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.

show abstract

Dendritic Cell Differentiation and Maturation in the Presence of HIV Type 2 Envelope

Cavaleiro

Baptista²,

Foxall³

et al. 2009

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

show abstract

Increased frequency of CD25dimCD4+ T-cells in HIV-2 infection, a naturally occurring attenuated form of HIV-1

Cited by 5 publications

References 43 publications

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation

Dendritic Cell Differentiation and Maturation in the Presence of HIV Type 2 Envelope

Contact Info

Product

Resources

About