Increased losses of CD4+CD45RA+ cells in late stages of HIV infection is related to increased risk of death

Ullum, Henrik; Lepri, Alessandro Cozzi; Victor, Jette; Skinhøj, Peter; Phillips, Andrew; Pedersen, Bente Klarlund

doi:10.1097/00002030-199712000-00012

Cited by 47 publications

(32 citation statements)

References 27 publications

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“…HIV infection in humans is characterized by a complex set of changes in lymphocyte subpopulations, including progressive diminution of CD4 ϩ T-cell number or percentages, progressive depletion of naive T cells, increased levels of activated CD8 ϩ cells, and loss of CD8 ϩ T cells expressing the costimulatory molecule CD28 (19,56,64). Immunophenotypic analyses of SIVmnd-2-infected and uninfected mandrills revealed only relatively minor, statistically insignificant changes in CD4 ϩ T-cell percentages on both compartments.…”

Section: Fig 5 Longitudinal Phenotypic Analysis Of Expression Of CDmentioning

confidence: 99%

Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills ( Mandrillus sphinx )

Onanga

Souquière

Makuwa

et al. 2006

J Virol

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Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4؉ and CD8 ؉ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virusinfected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10 7 to 10 8 RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10 5 to 10 6 RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10 5 to 10 6 DNA copies/10 6 cells) and stabilized at 10 3 to 10 4 DNA copies/10 6 cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3 ؉ CD4 ؉ cells in the LNs occurred in animals with high peak VLs. CD4؉ and CD8 ؉ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

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Section: Fig 5 Longitudinal Phenotypic Analysis Of Expression Of CDmentioning

confidence: 99%

Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills ( Mandrillus sphinx )

Onanga

Souquière

Makuwa

et al. 2006

J Virol

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“…These cells provide an essential resource both for mounting immune responses against novel Ags and also for maintaining T cell homeostasis. In HIV disease, the progressive depletion of naive CD4 ϩ and CD8 ϩ T cells (1) predicts clinical outcome (2) and responsiveness to immunization (3). Compounding the problems associated with the decline in naive T cell numbers, function of the remaining naive CD4 ϩ T cells is impaired in HIV-infected individuals (4).…”

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confidence: 99%

Impaired Induction of CD27 and CD28 Predicts Naive CD4 T Cell Proliferation Defects in HIV Disease

Luciano

Lederman

Valentin-Torres

et al. 2007

The Journal of Immunology

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Many immunological defects have been described in HIV disease, including a diminished capacity of naive CD4+ T cells to expand after TCR stimulation. The mechanisms underlying impaired naive CD4+ T cell expansion in HIV disease are not well described. Using a rigorous phenotypic definition of naive T cells, we found that cell cycle entry after TCR engagement was restricted to cells that increased surface expression of costimulatory molecules CD27 and CD28. Induction of these receptors, however, was not sufficient to result in cell cycle entry among the CD4+CD31− naive T cell subset. Analyses of cells from HIV-infected persons indicated that naive CD4+CD31+ T cells from these subjects were impaired in their ability to enter the cell cycle after stimulation and this impairment was predicted by the relatively poor induction of costimulatory molecules on these cells. Thus, failure to increase surface expression of costimulatory molecules may contribute to the naive T cell expansion failure that characterizes HIV infection.

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“…The loss of naive T cells could severely limit the capacity of patient immune systems to respond to novel Ags including those that may result from escape mutations by replicating HIV. Depletion of naive T cells appears to predict clinical outcome (6), responsiveness to therapy (7), and may also predict poor immunization responses by HIV-infected patients (8). Thus, naive T cell depletion in HIV disease has significant clinical implications.…”

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confidence: 99%

Impaired TCR-Mediated Induction of Ki67 by Naive CD4+ T Cells Is Only Occasionally Corrected by Exogenous IL-2 in HIV-1 Infection

Sieg

Bazdar

Lederman

2003

The Journal of Immunology

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Perturbations in naive T cell homeostasis and function may play a major role in the immunodeficiency that accompanies HIV infection. By examining naive CD4+ T cell function on a single cell basis, we provide evidence that these cells have significant qualitative defects in HIV disease. Ki67, a molecule expressed during cell cycle progression, is induced less efficiently among naive CD4+ T cells from HIV-infected individuals following activation with anti-TCR Ab. The impairment in Ki67 expression is evident even when a separate function, CD62L down-modulation, is within normal ranges. Moreover, the defects in Ki67 induction are only sometimes corrected by the addition of rIL-2 to cell cultures. An initial assessment of IL-2 unresponsiveness in cells from selected HIV-infected individuals suggests that the defect is not a consequence of impaired IL-2R expression or IL-2R signaling capability. Qualitative defects in naive T cells that cannot be routinely corrected by IL-2 have significant implications for disease pathogenesis and for strategies using IL-2 as a vaccine adjuvant in HIV disease.

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Increased losses of CD4+CD45RA+ cells in late stages of HIV infection is related to increased risk of death

Abstract: This study confirms a selective loss of memory CD4+ cells early in HIV infection followed by increased loss of naive CD4+ cells in later stages of the infection. The loss of naive CD4+ cells seems to be important in the pathogenesis of terminal HIV infection.

Cited by 47 publications

References 27 publications

Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills ( Mandrillus sphinx )

Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills ( Mandrillus sphinx )

Impaired Induction of CD27 and CD28 Predicts Naive CD4 T Cell Proliferation Defects in HIV Disease

Impaired TCR-Mediated Induction of Ki67 by Naive CD4+ T Cells Is Only Occasionally Corrected by Exogenous IL-2 in HIV-1 Infection

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