Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection

Hellerstein, Marc K.; Hoh, Rebecca; Hanley, Mary Beth; Cesar, Denise; Lee, Daniel; Neese, Richard A.; McCune, Joseph M.

doi:10.1172/jci17533

Cited by 122 publications

(179 citation statements)

References 36 publications

(131 reference statements)

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“…During chronic HIV infection, persistent viral replication coexists with high levels of CD8 ϩ T cell activation and turnover (41)(42)(43)(44)(45). We hypothesized that the loss of CD127 expression on CD8 ϩ T cells serves as a novel marker of the HIV-associated generalized immune activation and accelerated T cell turnover, and that in HIV-infected patients the chronic expansion of CD8 ϩ CD127…”

Section: Discussionmentioning

confidence: 99%

“…Third, the observation that CD8 ϩ CD127 Ϫ T cells isolated from healthy controls show reduced in vitro proliferative potential and increased susceptibility to apoptosis is consistent with the possibility that, in the setting of chronic HIV infection, the population of CD8 ϩ CD127 Ϫ cells is also characterized by short in vivo lifespan. In this case, these expanded CD8 ϩ CD127 Ϫ TE-like cells may include those fast-replicating and fast-dying CD8 ϩ T cells described recently in HIV-infected patients using in vivo T cell labeling with deuterium-based methods (45), as well as the fraction of CD8 ϩ T cells that appears to be exquisitely sensitive to apoptosis during HIV infection (47)(48)(49). Finally, the expansion of CD8 ϩ CD127 Ϫ TE-like cells that we observed in HIV-infected patients defined as normal progressors contrasts with what is seen in HIV-infected long-term nonprogressors (who maintain effective control of HIV replication in association with low levels of immune activation) in whom a substantial fraction of their HIV-specific CD8 ϩ T cells display functional features of TCM cells, such as a high proliferative response upon in vitro antigenic restimulation (50), thus supporting the possibility that an expansion of CD8 ϩ CD127 Ϫ TE-like cells reflects a pathogenic mechanism of immunodeficiency.…”

Section: Discussionmentioning

confidence: 99%

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Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals

Paiardini

Cervasi

Albrecht³

et al. 2005

The Journal of Immunology

211

182

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The immunodeficiency that follows HIV infection is related to the virus-mediated killing of infected CD4+ T cells, the chronic activation of the immune system, and the impairment of T cell production. In this study we show that in HIV-infected individuals the loss of IL-7R (CD127) expression defines the expansion of a subset of CD8+ T cells, specific for HIV as well as other Ags, that show phenotypic (i.e., loss of CCR7 and CD62 ligand expression with enrichment in activated and/or proliferating cells) as well as functional (i.e., production of IFN-γ, but not IL-2, decreased ex vivo proliferative potential and increased susceptibility to apoptosis) features of effector T cells. Importantly, in HIV-infected individuals the levels of CD8+CD127− T cells are directly correlated with the main markers of disease progression (i.e., plasma viremia and CD4+ T cell depletion) as well as with the indices of overall T cell activation. In all, these results identify the expansion of CD8+CD127− effector-like T cells as a novel feature of the HIV-associated immune perturbation. Further studies are thus warranted to determine whether measurements of CD127 expression on CD8+ T cells may be useful in the clinical management of HIV-infected individuals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals

Paiardini

Cervasi

Albrecht³

et al. 2005

The Journal of Immunology

211

182

View full text Add to dashboard Cite

show abstract

“…Additional mechanisms of CD4 T cell destruction, such as targeting by antibodies and by autoreactive T cells, have been described but are thought to make smaller contributions to the overall loss of CD4 T cells. In addition to increased CD4 T cell death induced by HIV, a decreased thymic output of naïve CD4 T cells in HIV-infected subjects results in an inability to replace CD4 T cells at the rate that they are destroyed (125,126). During the early stages of HIV infection, the CD4 T cell population in the intestinal lamina propria is depleted preferentially and markedly; a large fraction of the cells lost in this initial phase of infection are CD4 Th17 effector memory cells (31).…”

Section: Hiv Effects On Tb Immunity: Cd4 T Cell Depletionmentioning

confidence: 99%

HIV and Tuberculosis: a Deadly Human Syndemic

2011

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SUMMARY A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.

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“…In contrast, memory/effector CD4 T cells appear to proliferate substantially more, which is supported by the results of Ki67 staining and by the greater fraction of memory/effector CD4 T cells compared with naive CD4 T cells that incorporate in vivo label with stable isotopes. 26 Homeostatic proliferation increases dramatically with peripheral lymphopenia and/or reduced thymic output 27 and is associated with increased levels of IL-7 because of its reduced consumption by peripheral lymphocytes. The remaining lymphocytes are exposed to increased levels of IL-7, which appears to directly drive naive CD4 T-cell proliferation.…”

Section: Post-thymic Homeostasis Of Human Naive Cd4 T Cellsmentioning

confidence: 99%

Protein tyrosine kinase 7: a novel surface marker for human recent thymic emigrants with potential clinical utility

2011

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Recent thymic emigrants (RTEs) are antigenically naive T cells that have recently completed intrathymic maturation and have emigrated from the thymus to the periphery. RTEs are clinically and immunologically important as they are essential for maintaining peripheral T cells in sufficient numbers in order to recognize, by their abT-cell receptors (TCRs), a diverse array of foreign peptide antigens. However, RTE frequency and function has been poorly understood because of a lack of surface markers to distinguish them from older non-RTE naive T cells. This review summarizes the biology of the intrathymic generation and function of RTEs, including the recent identification of protein tyrosine kinase 7 (PTK7) as a novel marker for human RTEs of the CD4 (helper) T-cell lineage. PTK7 þ RTEs in adults have a reduced capacity for activationinduced proliferation and cytokine production (interleukin-2 and interferon-g) than older PTK7À naive CD4 T cells. Importantly, this immaturity in CD4 RTE effector function may contribute to the reduced adaptive immune responses observed in situations in which CD4 RTEs predominate, including the fetus, neonate and young infant, and following immune reconstitution, such as post-hematopoietic stem cell transplant. The ability to identify viable CD4 þ RTEs based on PTK7 surface staining may be particularly useful in the infant for better defining the impact of nutritional and environmental factors on thymic output, peripheral T-cell function and adaptive immune responses to vaccination and infection.

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Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection

Cited by 122 publications

References 36 publications

Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals

Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals

HIV and Tuberculosis: a Deadly Human Syndemic

Protein tyrosine kinase 7: a novel surface marker for human recent thymic emigrants with potential clinical utility

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