Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans

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

doi:10.1038/4772

Cited by 535 publications

(463 citation statements)

References 26 publications

Supporting

Mentioning

422

Contrasting

Unclassified

Order By: Relevance

“…However, the pool of naïve CD8 + T cells is not increased because of their rapid maturation and transfer to the antigen-experienced compartment. This series of events is consistent with a high rate of lymphocyte turnover in patients with cancer, not unlike that seen in patients with HIV (Mohri et al, 1998;Hellerstein et al, 1999). The obvious downside of such rapid turnover in T cells is that the normal processes of maturation and differentiation of effector cells are disturbed, possibly leading to ineffective immune responses.…”

Section: Discussionsupporting

confidence: 71%

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

et al. 2003

View full text Add to dashboard Cite

A subset of circulating T cells (CD8 + CD45RO À CD27 À ) with a naïve phenotype, but mediating effector function, is considered to play an important role in host antitumour defence. To investigate the attributes of these effector T cells in patients with squamous cell carcinoma (SCC) of the head and neck cancer, venous blood was obtained from 39 individuals with cancer and 45 normal controls (NC). Peripheral blood mononuclear cells were isolated, stained with labelled monoclonal antibodies specific for CD8, CD45RO, CD45RA, CD62L, CD27, TCR-z as well as isotype controls and examined by multicolour flow cytometry. Annexin V binding to CD8 + T cells and PMA/ionomycin-induced IFN-g expression were also evaluated in patients and NC. The proportions of CD45RA + CD45RO À (naïve) and CD45RA À CD45RO + (memory) cells were found to be comparable within the CD8 + T-cell subset. However, relative to NC, the frequency of effector CD8 + CD45RO À CD27 À cells was strikingly increased in all SCC patients regardless of the disease status (P ¼ 0.0003). The proportion of these cells was found to increase with age in both patients and NC. In NC, stimulated IFN-g expression was largely restricted to CD8 + CD45RO À CD27 + cells, while in patients CD8 + CD45RO À CD27 À expressed IFN-g after ex vivo stimulation. Expression of the TCR-associated z chain was decreased or absent in freshly isolated CD8 + CD45RO À CD27 À T cells in patients (Po0.0001). Annexin V was found to bind to a higher proportion of circulating CD8 + T cells in patients than NC (Po0.006), and significantly more Annexin V + T cells were present in the effector (Po0.0059) than the naïve subset within the CD8 + CD45RO À compartment. The data indicate that the expanded CD8 + CD45RO À CD27 À T cells, which contain precursors of IFN-g-producing T cells, are z-negative and sensitive to apoptosis in the circulation of patients with HNC.

show abstract

Section: Discussionsupporting

confidence: 71%

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

et al. 2003

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

“…In the absence of exogenous antigen, memory and even naïve T cells exhibit a constant turnover. The daily replacement rate of T cells has been estimated to be on the order of 1%, which means that with about 3×10 11 T cells in a human body, approximately 3×10 9 T cells have to be generated each day Hellerstein et al, 1999;Neese et al, 2002). Memory T cells have higher homeostatic proliferation than naïve T cells , raising the question of whether they can out compete naïve T cells and, over time, significantly compromise the integrity of the naïve T-cell compartment.…”

mentioning

confidence: 99%

Aging and T-cell diversity☆

Goronzy

Lee

Weyand

2007

Experimental Gerontology

233

187

View full text Add to dashboard Cite

Naïve and memory CD4 and CD8 T cells represent a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T cells. Homeostatic control mechanisms are very effective to maintain a large and diverse subset of naïve CD4 T cells for many years up to the 8 th decade of life, but eventually and abruptly fail at about the age of 75 years. In contrast, the CD8 T cell compartment is more unstable, with progressive diminution of naïve T cells and increasing loss of diversity already during mid adulthood. Vaccination strategies need to aim at developing a broad repertoire of memory T cells before the critical time period when the naïve CD4 T-cell repertoire collapses. Research efforts need to aim at understanding the homeostatic control mechanisms to ultimately expand the time period of repertoire stability.Adaptive immune responses are initiated when T cells recognize endogenous antigen on activated and mature antigen-presenting cells. Successful responses depend on the repertoire of existing T cells (Nikolich-Zugich et al., 2004). The diversity of the T-cell compartment determines whether T cells are available that recognize antigen with high avidity. The frequency of each T-cell specificity in the existing repertoire influences how fast an initial immune recognition event can be amplified to generate a sufficient number of effector cells. Consequently, the naïve T-cell repertoire is highly diverse, providing the ability to recognize the universe of exogenous and potentially dangerous antigens. In contrast, the memory T-cell repertoire is selected by previous antigen exposure. Each memory T cell clone is present in larger frequency, guaranteeing a more rapid response upon re-exposure to the same antigen. Homeostatic regulation is important not only to control the size of the T-cell compartment, but also the composition of naïve and memory T cells, as well as the diversity of each T-cell compartment (Goldrath and Bevan, 1999a). T cell homeostasis and ageThe homeostatic control mechanisms have to deal with exogenous and endogenous challenges (Freitas and Rocha, 2000;Jameson, 2002). The T-cell compartment is a highly dynamic T-cell reservoir with sometimes conflicting kinetics of singular components that compete for space. The most evident example is the clonal expansion that occurs after naïve or memory T cells encounter antigen. This clonal expansion is dramatic and has been estimated to include 10 to 15 population doublings followed by equally rapid clonal contraction with a majority of *Corresponding author. Mailing address: Lowance Center for Human Immunology, Emory University School of Medicine, 101 Woodruff Circle #1003, Atlanta, GA 30322. Phone: (404) 727-7310. Fax: (404) 727-7371. E-mail: E-mail: jgoronz@emory.edu.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As...

show abstract

Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans

Cited by 535 publications

References 26 publications

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

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

Aging and T-cell diversity☆

Contact Info

Product

Resources

About