Factors influencing T-cell turnover in HIV-1–seropositive patients

McCune, Joseph M.; Hanley, Mary Beth; Cesar, Denise; Halvorsen, Robert A.; Hoh, Rebecca; Schmidt, David J.; Wieder, Eric; Deeks, Steven G.; Siler, Scott Q.; Neese, Richard A.; Hellerstein, Marc K.

doi:10.1172/jci8647

Cited by 217 publications

(276 citation statements)

References 29 publications

(74 reference statements)

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“…47 In HIV-1 infected adults on antiretroviral therapy, deuterated glucose measurements indicate that the half-lives of naive-phenotype T cells ranges from 116 to more than 365 days, whereas T cells of the memory/effector-phenotype persisted with half-lives from 22 to 79 days. 48 T cells are different from most other tissues such as in the case of red blood cells where survival is related to lifespan of the cells and the oldest cells are removed first. The majority of T cells induced following an antigenic challenge die while still 'young' through activation-induced cell death, as a consequence of the need to maintain T-cell homeostasis both at the total population number as well as at the clonal level.…”

Section: Engraftmentmentioning

confidence: 98%

T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

Porter

June

2005

Bone Marrow Transplant

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Summary:Adoptive immunotherapy is the isolation and infusion of antigen-specific or nonspecific lymphocytes. Adoptive therapy with T cells may have a role in replacing, repairing, or enhancing immune function damaged by cytotoxic therapies, and rapid lymphocyte recovery may improve outcome after autologous and allogeneic stem cell transplantation (SCT). Recently, a plethora of information on the basic mechanisms of T-cell biology and regulation of cellular immune responses has emerged, permitting the development of new forms of adoptive cell therapy. Efficient ex vivo culture method for T-cell subsets affords the possibility of adoptive transfer of T cells engineered with enhanced capacity for central memory, effector cytotoxicity, Th1, Th2, veto cell, and T regulatory functions. Studies show that homeostatic Tcell proliferation is important for effective adoptive immunotherapy and pretreatment with chemotherapy may enhance the effects of infused T cells. Replicative senescence, in part due to telomere erosion, likely limits successful adoptive immunotherapy, though it may be possible to maintain T-cell pools by enforced expression of telomerase. Clinical trials now demonstrate that it is possible to enhance immune reconstitution after SCT with cytokines or infusions of ex vivo costimulated expanded T cells. These data all support the premise that adoptive therapy can accelerate reconstitution of cellular immunity with enhanced antitumor effects following SCT. Bone Marrow Transplantation (2005) 35, 935-942.

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Section: Engraftmentmentioning

confidence: 98%

T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

Porter

June

2005

Bone Marrow Transplant

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“…In vivo studies of T-cell dynamics in chronic HIV infection, using methods of direct DNA labeling of proliferating cells with stable deuterium isotope, have shown a state of high turnover of both CD4 and CD8 T cells and a decrease in memory CD4 and CD8 T cell half-life. 15,16 This was associated with persistent high viral load and was markedly reduced after initiation of HAART. [16][17][18] This concept of high turnover involves increased T-cell activation, expansion, shift from naive to memory/effector stage and activationinduced cell death.…”

Section: During Chronic Infectionmentioning

confidence: 99%

To kill or be killed: how HIV exhausts the immune system

Gougeon

2005

Cell Death Differ

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“…BrdU 1 cells can be easily detected by flow cytometry, and BrdU labelling has been widely used to study lymphocyte kinetics in animals (Gratzner 1982;Penit & Vasseur 1988;Forster et al 1989;Forster & Rajewsky 1990;Rocha et al 1990;Schittek & Rajewsky 1990;Tough & Sprent 1994Dolbeare 1995;Zimmerman et al 1996;Mohri et al 1998;Bonhoeffer et al 2000;Kovacs et al 2001). Cellular turnover rates in man have also been studied by the administration of deuterated glucose ( 2 H-glucose), which leads to deuterium being incorporated into the DNA of dividing cells (Macallan et al 1998;Hellerstein 1999;Hellerstein et al 1999;McCune et al 2000;Mohri et al 2001;Ribeiro et al 2002a,b).…”

Section: Introductionmentioning

confidence: 99%

Estimating average cellular turnover from 5–bromo–2'–deoxyuridine (BrdU) measurements

Boer

Mohri

et al. 2003

Proc. R. Soc. Lond. B

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Cellular turnover rates in the immune system can be determined by labelling dividing cells with 5-bromo-29-deoxyuridine (BrdU) or deuterated glucose ( 2 H-glucose). To estimate the turnover rate from such measurements one has to fit a particular mathematical model to the data. The biological assumptions underlying various models developed for this purpose are controversial. Here, we fit a series of different models to BrdU data on CD4 1 T cells from SIV 2 and SIV 1 rhesus macaques. We first show that the parameter estimates obtained using these models depend strongly on the details of the model. To resolve this lack of generality we introduce a new parameter for each model, the 'average turnover rate', defined as the cellular death rate averaged over all subpopulations in the model. We show that very different models yield similar estimates of the average turnover rate, i.e. ca. 1% day 2 1 in uninfected monkeys and ca. 2% day 2 1 in SIV-infected monkeys. Thus, we show that one can use BrdU data from a possibly heterogeneous population of cells to estimate the average turnover rate of that population in a robust manner.

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Factors influencing T-cell turnover in HIV-1–seropositive patients

Cited by 217 publications

References 29 publications

T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

To kill or be killed: how HIV exhausts the immune system

Estimating average cellular turnover from 5–bromo–2'–deoxyuridine (BrdU) measurements

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