In patients on prolonged HAART, a significant pool of HIV infected CD4 T cells are HIV-specific

Demoustier, Audrey; Gubler, Brigitte; Lambotte, Olivier; Goër, Marie-Ghislaine de; Wallon, Christine; Goujard, Cécile; Delfraissy, Jean‐François; Taoufik, Yassine

doi:10.1097/00002030-200209060-00006

Cited by 43 publications

(44 citation statements)

References 30 publications

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“…The responding HIV-specific CD4 ϩ T cells sorted from these two individuals were infected at frequencies similar to those of other memory CD4 ϩ T cells, demonstrating that the HIV-specific CD4 ϩ T cells of these two subjects were not preferentially infected by HIV. In contrast, and consistent with our previous studies and those of others (11,14,17), the HIV-specific CD4 ϩ T cells from subject 19 were preferentially infected ( Table 2).…”

Section: T Cells In Hivsupporting

confidence: 92%

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Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4⁺T Cells In Vivo

Brenchley¹,

Ruff²,

Casazza

et al. 2006

J Virol

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CD4 ؉ T-cell help is essential for effective immune responses to viruses. In human immunodeficiency virus (HIV) infection, CD4؉ T cells specific for HIV are infected by the virus at higher frequencies than other memory CD4 ؉ T cells. Here, we demonstrate that HIV-specific CD4 ؉ T cells are barely detectable in most infected individuals and that the corresponding CD4 ؉ T cells exhibit an immature phenotype compared to both cytomegalovirus (CMV)-specific CD4؉ T cells and other memory CD4 ؉ T cells. However, in two individuals, we observed a rare and diametrically opposed pattern in which HIV-specific CD4 ؉ T-cell populations of large magnitude exhibited a terminally differentiated immunophenotype; these cells were not preferentially infected in vivo. Clonotypic analysis revealed that the HIV-specific CD4 ؉ T cells from these individuals were crossreactive with CMV. Thus, preferential infection can be circumvented in the presence of cross-reactive CD4 ؉ T cells driven to maturity by coinfecting viral antigens, and this physical proximity rather than activation status per se is an important determinant of preferential infection based on antigen specificity. These data demonstrate that preferential infection reduces the life span of HIV-specific CD4 ؉ T cells in vivo and thereby compromises the generation of effective immune responses to the virus itself; further, this central feature in the pathophysiology of HIV infection can be influenced by the cross-reactivity of responding CD4 ؉ T cells.

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Section: T Cells In Hivsupporting

confidence: 92%

“…While HIV-specific CD4 ϩ T cells are paramount in control of viral replication, these cells are preferentially infected by the virus at all stages of infection (11,14,17).…”

Section: Cd4mentioning

confidence: 99%

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4⁺T Cells In Vivo

Brenchley¹,

Ruff²,

Casazza

et al. 2006

J Virol

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“…A fuller appreciation of infection within these compartments may lead to a better understanding of HIV disease pathogenesis and events that result in latent infection (13,20). For example, it has been shown that memory CD4 ϩ T cells specific for HIV are preferentially infected by the virus, which may contribute to the loss of HIV-specific CD4 ϩ T-cell responses (14,17,24). Furthermore, it has been shown that developing thymocytes at the CD4 ϩ CD8 ϩ double-positive stage can become infected by HIV and thus might contribute to infection of the peripheral naïve CD4 ϩ and CD8 ϩ T-cell pools (7,9,25,28,33,34,38,44).…”

Section: Although Human Immunodeficiency Virus Type 1 (Hiv-1) Infectimentioning

confidence: 99%

T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis

Brenchley¹,

Hill²,

Ambrozak³

et al. 2004

J Virol

346

298

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Identification of T-cell subsets that are infected in vivo is essential to understanding the pathogenesis of human immunodeficiency virus (HIV) disease; however, this goal has been beset with technical challenges. Here, we used polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity, followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show that resting memory CD4 ؉ T cells are the predominantly infected cells but that terminally differentiated memory CD4؉ T cells contain 10-fold fewer copies of HIV DNA. Memory CD8 ؉ T cells can also be infected upon upregulation of CD4; however, this is infrequent and HIV-specific CD8 ؉ T cells are not infected preferentially. Naïve CD4 ؉ T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from naïve CD8 ؉ T cells, suggesting that the thymus is not a major source of HIV-infected T cells in the periphery. These data illuminate the underlying mechanisms that distort T-cell homeostasis in HIV infection.

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“…On the one hand, increased HIV-1 endocytosis is expected to boost the priming of anti-HIV lymphocytes, as well as the activation of anti-HIV memory lymphocytes, strengthening the anti-HIV immune response. On the other hand, this phenomenon could also favor the spread of HIV as a consequence of the increased number of activated anti-HIV CD4 1 lymphocytes, which are the preferential targets of HIV [38][39][40]. In sum, our results suggest that cell-to-cell contact-dependent HIV endocytosis by DC could be an efficient mechanism of induction of anti-HIV adaptive immunity in vivo.…”

Section: Discussionmentioning

confidence: 63%

DC contact with HIV‐1‐infected cells leads to high levels of Env‐mediated virion endocytosis coupled with enhanced HIV‐1 Ag presentation

et al. 2009

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In HIV-infected patients, DC are likely to interact with both cell-free HIV and HIV-infected cells. We were interested in investigating the mechanism of virus transmission occurring upon contact between HIV-1-infected cells and DC, as well as the consequences for HIV-1 Ag-presenting activity. By comparing mixed co-cultures with trans-well cultures, we observed that cell-to-cell contact strongly increased HIV-1 Env-mediated virion endocytosis in target DC. This endocytosis was independent of HIV-1 tropism, de novo infection, HIV-1 Env-CD4-dependent fusion, and immature DC activation/maturation. We also found that augmentation of HIV-1 endocytosis was closely correlated with strong, Env-dependent HIV-1 Ag presentation by DC. Our results provide a better understanding of the mechanisms underlying the induction of the anti-HIV adaptive immune response. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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In patients on prolonged HAART, a significant pool of HIV infected CD4 T cells are HIV-specific

Cited by 43 publications

References 30 publications

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4⁺T Cells In Vivo

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4⁺T Cells In Vivo

T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis

DC contact with HIV‐1‐infected cells leads to high levels of Env‐mediated virion endocytosis coupled with enhanced HIV‐1 Ag presentation

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In patients on prolonged HAART, a significant pool of HIV infected CD4 T cells are HIV-specific

Cited by 43 publications

References 30 publications

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4+T Cells In Vivo

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4+T Cells In Vivo

T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis

DC contact with HIV‐1‐infected cells leads to high levels of Env‐mediated virion endocytosis coupled with enhanced HIV‐1 Ag presentation

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Product

Resources

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Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4⁺T Cells In Vivo

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4⁺T Cells In Vivo