scholarly journals Rapid Turnover of Effector–Memory CD4+ T Cells in Healthy Humans

2004 ◽  
Vol 200 (2) ◽  
pp. 255-260 ◽  
Author(s):  
Derek C. Macallan ◽  
Diana Wallace ◽  
Yan Zhang ◽  
Catherine de Lara ◽  
Andrew T. Worth ◽  
...  

Memory T cells can be divided into central–memory (TCM) and effector–memory (TEM) cells, which differ in their functional properties. Although both subpopulations can persist long term, it is not known whether they are maintained by similar mechanisms. We used in vivo labeling with deuterated glucose to measure the turnover of CD4+ T cells in healthy humans. The CD45R0+CCR7− TEM subpopulation was shown to have a rapid proliferation rate of 4.7% per day compared with 1.5% per day for CD45R0+CCR7+ TCM cells; these values are equivalent to average intermitotic (doubling) times of 15 and 48 d, respectively. In contrast, the CD45RA+CCR7+ naive CD4+ T cell population was found to be much longer lived, being labeled at a rate of only 0.2% per day (corresponding to an intermitotic time of approximately 1 yr). These data indicate that human CD4+ TEM cells constitute a short-lived cell population that requires continuous replenishment in vivo.

2007 ◽  
Vol 179 (7) ◽  
pp. 4397-4404 ◽  
Author(s):  
Stephen L. Shiao ◽  
Nancy C. Kirkiles-Smith ◽  
Benjamin R. Shepherd ◽  
Jennifer M. McNiff ◽  
Edward J. Carr ◽  
...  

2013 ◽  
Vol 156 (1-2) ◽  
pp. 82-93 ◽  
Author(s):  
Masahiro Takahara ◽  
Yasuhiro Nemoto ◽  
Shigeru Oshima ◽  
Yu Matsuzawa ◽  
Takanori Kanai ◽  
...  

2007 ◽  
Vol 248 (2) ◽  
pp. 77-85 ◽  
Author(s):  
Madoka Koyanagi ◽  
Kenji Fukada ◽  
Takehiko Uchiyama ◽  
Junji Yagi ◽  
Yutaka Arimura

2018 ◽  
Vol 21 (04) ◽  
pp. 771-781
Author(s):  
Mousa Komai Koma

Objective: Ligation of TLR by distinct pathogen components provides essentialsignals for T cell priming, although how individual TLR engagement affects memory T cellsinduction and maintenance in vivo is not well defined. The aim of the present study was toinvestigate the role of TLR2 engagement in the maintenance of memory T cells. Method: Ovaspecific KJ-1 cells from DO-11 mice were adoptively transferred to Balb/c mice. T cells wereactivated with Ova in the host of adoptive cells to induce memory. To examine the function and+ maintenance of memory cells in vivo, CD4 T cells were transferred to mice, which were thenchallenged with Ova-BLP and looked for memory cell proliferation. Furthermore, the memory Tcells harvested from lymph node and spleen of Balb/c mice were treated with Ova and BLP in vitroto establish the effects of TLR2 ligation on proliferation of memory T cells. Two different protocolswere used to confirm the same phenomenon. Results: Two different protocols show thatmemory T cells proliferation in vivo and in vitro can be maintained by TLR2 agonist (BLP). Wedemonstrate that antigen specific CD4 T cells undergo extensive proliferation in the presence ofOva and TLR2 agonist, in fact with TLR2 priming results in greater expansion. Moreover, TLR2agonist priming of ova-specific CD4 T cells resulted in a higher frequency of persisting ova/BLPspecific memory CD4 T cells which facilitated strong secondary responses upon challenge withova antigen. Conclusions: Ligation of TLR2 agonist BLP (Pam3Cys) alone is sufficient to+ maintain the proliferation of Ova specific CD4 T cells without the need of antigen. Which mightsuggest that long-term functional capacities of T cells are set by innate signals during earlyphases of an infection


2021 ◽  
Vol 22 (2) ◽  
pp. 912
Author(s):  
Nabila Seddiki ◽  
John Zaunders ◽  
Chan Phetsouphanh ◽  
Vedran Brezar ◽  
Yin Xu ◽  
...  

HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4+ T cells in peripheral blood, which highly express the α-chain of the IL-7 receptor (CD127), but not CD38 or Ki-67, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease very early in HIV-1 infection. Indeed, CD73+ memory CD4+ T cells comprised a median of 7.5% (interquartile range: 4.5–10.4%) of CD4+ T cells in peripheral blood from healthy adults, but were decreased in primary HIV-1 infection to a median of 3.7% (IQR: 2.6–6.4%; p = 0.002); and in chronic HIV-1 infection to 1.9% (IQR: 1.1–3%; p < 0.0001), and were not restored by antiretroviral therapy. Moreover, we found that a significant proportion of CD73+ memory CD4+ T cells were skewed to a gut-homing phenotype, expressing integrins α4 and β7, CXCR3, CCR6, CD161 and CD26. Accordingly, 20% of CD4+ T cells present in gut biopsies were CD73+. In HIV+ subjects, purified CD73+ resting memory CD4+ T cells in PBMC were infected with HIV-1 DNA, determined by real-time PCR, to the same level as for purified CD73-negative CD4+ T cells, both in untreated and treated subjects. Therefore, the proliferative CD73+ subset of memory CD4+ T cells is disproportionately reduced in HIV-1 infection, but, unexpectedly, their IL-7 dependent long-term resting phenotype suggests that residual infected cells in this subset may contribute significantly to the very long-lived HIV proviral DNA reservoir in treated subjects.


Tuberculosis ◽  
2011 ◽  
Vol 91 (3) ◽  
pp. 224-230 ◽  
Author(s):  
L. El Fenniri ◽  
Z. Toossi ◽  
H. Aung ◽  
G. El Iraki ◽  
J. Bourkkadi ◽  
...  

2017 ◽  
Vol 3 (3) ◽  
Author(s):  
Kathleen M. Gilbert ◽  
Sarah J. Blossom ◽  
Brad Reisfeld ◽  
Stephen W. Erickson ◽  
Kanan Vyas ◽  
...  

2001 ◽  
Vol 194 (9) ◽  
pp. 1349-1360 ◽  
Author(s):  
Maria A. Curotto de Lafaille ◽  
Stephanie Muriglan ◽  
Mary-Jean Sunshine ◽  
Ying Lei ◽  
Nino Kutchukhidze ◽  
...  

A key event in the pathogenesis of allergies is the production of antibodies of the immunoglobulin (Ig)E class. In normal individuals the levels of IgE are tightly regulated, as illustrated by the low serum IgE concentration. In addition, multiple immunizations are usually required to generate detectable IgE responses in normal experimental animals. To define the parameters that regulate IgE production in vivo, we generated mice bearing monoclonal populations of B and T lymphocytes specific for influenza virus hemagglutinin (HA) and chicken ovalbumin (OVA), respectively. A single immunization of the monoclonal mice with the cross-linked OVA-HA antigen led to serum IgE levels that reached 30–200 μg/ml. This unusually high IgE response was prevented by the infusion of regulatory α/β CD4+ T cells belonging to both CD25+ and CD25− subpopulations. The regulation by the infused T cells impeded the development of fully competent OVA-specific effector/memory Th2 lymphocytes without inhibiting the initial proliferative response of T cells or promoting activation-induced cell death. Our results indicate that hyper IgE responses do not occur in normal individuals due to the presence of regulatory T cells, and imply that the induction of regulatory CD4+ T cells could be used for the prevention of atopy.


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