Lymphocyte kinetics in health and disease

Asquith, Becca; Borghans, José A. M.; Ganusov, Vitaly V.; Macallan, Derek C.

doi:10.1016/j.it.2009.01.003

Cited by 32 publications

(35 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data from the current study suggest that this difference could relate to the relative importance of homeostatic forces in the regulation of these two pools. Homeostatic forces likely are regulated to allow only a limited degree of expansion for each individual cell so as to preserve diversity of the repertoire (32,33). It is probable that there is no such restriction for Agdriven/inflammatory responses of the CD4 or CD8 pools.…”

Section: Discussionmentioning

confidence: 99%

CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles of Homeostasis, HIV, Type I IFN, and IL-7

Catálfamo

Wilhelm

Tcheung

et al. 2011

The Journal of Immunology

112

View full text Add to dashboard Cite

Immune activation plays an important role in the pathogenesis of HIV disease. Although the causes are not fully understood, the forces that lead to immune dysfunction differ for CD4 and CD8 T cells. In this study, we report that the molecular pathways that drive immune activation during chronic HIV infection are influenced by differences in the homeostatic regulation of the CD4 and CD8 T cell pools. Proliferation of CD4 T cells is controlled more tightly by CD4 T cell numbers than is CD8 T cell proliferation. This difference reflects the importance of maintaining a polyclonal CD4 T cell pool in host surveillance. Both pools of T cells were found to be driven by viral load and its associated state of inflammation. In the setting of HIV-induced lymphopenia, naive CD4 T cells were recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8 T cell proliferation was driven mainly by levels of HIV RNA. RNA analysis revealed increased expression of genes associated with type I IFN and common γ chain cytokine signaling in CD4 T cell subsets and only type I IFN-associated genes in CD8 T cell subsets. In vitro studies demonstrated enhanced STAT1 phosphorylation in response to IFN-α and increased expression of the IFNAR1 transcripts in naive and memory CD4 T cells compared with that observed in CD8 T cells. CD4 T cell subsets also showed enhanced STAT1 phosphorylation in response to exogenous IL-7.

show abstract

Section: Discussionmentioning

confidence: 99%

CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles of Homeostasis, HIV, Type I IFN, and IL-7

Catálfamo

Wilhelm

Tcheung

et al. 2011

The Journal of Immunology

112

View full text Add to dashboard Cite

show abstract

“…Alterations of the system and observation of the responses to perturbations is also a way to understand the systems properties. As stated before, modelling cell population dynamics is an active field of research in systems immunology and a plenty of model of T cell dynamics have been proposed (Mehr, Globerson et al 1995;Mehr, Perelson et al 1997;Efroni, Harel et al 2007;Asquith, Borghans et al 2009;Dowling and Hodgkin 2009;Souza-e-Silva, Savino et al 2009). Our mathematical model of T cell dynamics is based on a conveyor-belt model of differentiation (ThomasVaslin, Altes et al 2008) as summarised below in Figure 4.…”

Section: Immunosuppression and Aging: Some Examplesmentioning

confidence: 99%

Immunodepression and Immunosuppression During Aging

Thomas‐Vaslin¹,

Six²,

Pham³

et al. 2012

Immunosuppression - Role in Health and Diseases

View full text Add to dashboard Cite

show abstract

“…2 Studies based on deuterated glucose, which is typically administered for shorter periods than 2 H 2 O, have consistently yielded shorter average life spans than studies based on heavy water. 2 Although it cannot be excluded that a difference between the 2 H-labeled compounds may have an influence, 1 the correlation between the expected life span and the length of the labeling period remained when comparing life span estimates derived from glucose labeling or water labeling separately. 2 This finding suggests that at least some of the discrepancy between estimated T-cell life spans from stable isotope-labeling studies is attributable to the duration of label administration.…”

Section: Introductionmentioning

confidence: 99%

Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans

Westera

Drylewicz

Braber

et al. 2013

Blood

Self Cite

121

165

View full text Add to dashboard Cite

Key Points• Life span estimates can be sensitive to the duration of stable isotope label administration, explaining discrepancies in the literature.• Multiexponential models are needed to obtain reliable leukocyte life span estimates.Quantitative knowledge of the turnover of different leukocyte populations is a key to our understanding of immune function in health and disease. Much progress has been made thanks to the introduction of stable isotope labeling, the state-of-the-art technique for in vivo quantification of cellular life spans. Yet, even leukocyte life span estimates on the basis of stable isotope labeling can vary up to 10-fold among laboratories. We investigated whether these differences could be the result of variances in the length of the labeling period among studies. To this end, we performed deuterated water-labeling experiments in mice, in which only the length of label administration was varied. The resulting life span estimates were indeed dependent on the length of the labeling period when the data were analyzed using a commonly used single-exponential model. We show that multiexponential models provide the necessary tool to obtain life span estimates that are independent of the length of the labeling period. Use of a multiexponential model enabled us to reduce the gap between human T-cell life span estimates from 2 previously published labeling studies. This provides an important step toward unambiguous understanding of leukocyte turnover in health and disease. (Blood. 2013;122(13):2205-2212

show abstract

Lymphocyte kinetics in health and disease

Cited by 32 publications

References 56 publications

CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles of Homeostasis, HIV, Type I IFN, and IL-7

CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles of Homeostasis, HIV, Type I IFN, and IL-7

Immunodepression and Immunosuppression During Aging

Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans

Contact Info

Product

Resources

About