ArticleThe Journal of experimental medicine2007
Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection.
Article in The Journal of experimental medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 166 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
166 citing papers in PubMed, 1 synthesis or guideline pooled it, 276 citations in OpenAlex.
- The Hitchhiker Guide to CD4Frontiers in immunology · 2021Pooled it
- Trial
- Trial
- Englumafusp alfa plus glofitamab in B cell non-Hodgkin lymphoma: a phase 1 trial.Nature medicine · 2026Article
- Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART.Immunity & ageing : I & A · 2025Article
- The prognosis for delayed immune recovery in HIV-infected children might be associated with pre-cART CD4BMC research notes · 2025Article
- Central Memory CD4 T Cells from Persons with HIV Accumulate DNA Content Defects During Proliferative Response.AIDS research and human retroviruses · 2025Article
- Impact of alemtuzumab-mediated lymphocyte depletion on SIV reservoir establishment and persistence.PLoS pathogens · 2024Article
- Review
- The Prognosis for Delayed Immune Recovery in HIV-Infected Children might be Associated with Pre-cART CD4 + T cell Count Irrespective of Co-Infection with Tuberculosis.Research square · 2024Article
- Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir.PLoS pathogens · 2024Article
- Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence.Nature communications · 2023Article
- Programming cytomegalovirus as an HIV vaccine.Trends in immunology · 2023Review
- Prolonged experimental CD4Nature communications · 2023Article
- Highly dampened HIV-specific cytolytic effector T cell responses define viremic non-progression.Immunobiology · 2022Article
- Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.Nature communications · 2022Article
- The ingenol-based protein kinase C agonist GSK445A is a potent inducer of HIV and SIV RNA transcription.PLoS pathogens · 2022Article
- Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.PLoS pathogens · 2021Article
- CD8+ T cells fail to limit SIV reactivation following ART withdrawal until after viral amplification.The Journal of clinical investigation · 2021Article
- Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4(+) CCR5(+) effector-memory T (T(EM)) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4(+) memory T cell proliferation appears to prevent collapse of effector site CD4(+) T(EM) cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4(+) T(EM) cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4(+) T(EM) cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4(+) T(EM) cells from central-memory T (T(CM)) cell precursors. The instability of effector site CD4(+) T(EM) cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5(-) CD4(+) T(CM) cells. These data suggest that although CD4(+) T(EM) cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4(+) T(CM) cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.