scholarly journals MAINTENANCE OF MEMORY CD4 CELLS

2018 ◽  
Vol 21 (04) ◽  
pp. 771-781
Author(s):  
Mousa Komai Koma
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Memory Cell ◽  
Tlr2 Agonist ◽  
Functional Capacities ◽  
Memory Cd4 T Cells

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

scholarly journals CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection

2021 ◽  
Vol 22 (2) ◽  
pp. 912
Author(s):  
Nabila Seddiki ◽  
John Zaunders ◽  
Chan Phetsouphanh ◽  
Vedran Brezar ◽  
Yin Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Significant Proportion ◽  
Long Term Memory ◽  
Ki 67 ◽  
Memory Cd4 T Cells ◽  
Hiv 1

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.

scholarly journals Human Effector Memory CD4+ T Cells Directly Recognize Allogeneic Endothelial Cells In Vitro and 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 ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Cd4 T Cells ◽  
Effector Memory ◽  
Memory Cd4 T Cells

scholarly journals IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice

2013 ◽  
Vol 156 (1-2) ◽  
pp. 82-93 ◽  
Author(s):  
Masahiro Takahara ◽  
Yasuhiro Nemoto ◽  
Shigeru Oshima ◽  
Yu Matsuzawa ◽  
Takanori Kanai ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Effector Memory ◽  
Chronic Colitis ◽  
Memory Cd4 T Cells ◽  
In Vitro Survival ◽  
Memory Subset

scholarly journals ID:3002 Notch-mediated control of memory T cells against cancer cells

2017 ◽  
Vol 4 (S) ◽  
pp. 12
Author(s):  
Koji Yasutomo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Term Survival ◽  
Long Term Survival ◽  
Memory Cd4 T Cells

T cells recognize an antigen presented by self-MHC, and the part of initially activated T cells differentiate toward memory T cells. T cells also recognize cancer cells leading to generation of memory T cells against cancer-derived antigens although the activity of T cells are frequently suppressed by various factors. The release from T cell inhibitory factors could allow T cells to respond to cancer cells. However, it remains unclear which molecules are required for long-term survival of memory T cells and generation of memory T cells against cancer cells. Notch functions as a regulator for fate decision, activation and survival of immune cells. We have demonstrated the roles of Notch in mature T cell differentiation and found that Notch signaling is essential for the maintenance of memory CD4 T cells. The inhibition of Notch disturbs the survival of memory CD4 T cells. The effect of Notch on T cell survival depended on glucose uptake through cell surface Glut1 expression. We revealed that Notch is crucial for the long-term survival of memory T cells against cancer cells and suppression of Notch signaling reduced the tumor antigen-specific killing of cancer cells. Those data demonstrate that Notch is pivotal for the maintenance of memory T cells against cancer cells and suggest that activation of Notch signaling might be advantageous to cancer immunotherapy.

scholarly journals Triggering DTH and CTL Activity by fd Filamentous Bacteriophages: Role of CD4+ T Cells in Memory Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Giovanna Del Pozzo ◽  
Dina Mascolo ◽  
Rossella Sartorius ◽  
Alessandra Citro ◽  
Pasquale Barba ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Long Term Memory ◽  
Short Term ◽  
Filamentous Bacteriophages ◽  
Ctl Responses

The ability of fd bacteriophage particles to trigger different arms of the immune system has been previously shown by us with particular emphasis on the ability of phages to raise CTL responses in vitro and in vivo. Here we show that fd virions in the absence of adjuvants are able to evoke a DTH reaction mediated by antigen specific CD8+ T cells. In addition, we analyzed the induction of CTL responses in mice depleted of CD4+ T cells, and we observed that short-term secondary CTL responses were induced in the absence of CD4+ T cells while induction of long-term memory CTLs required the presence of CD4+ T lymphocytes. These results examine the cellular mechanism at the basis of fd efficiency and provide new elements to further validate the use of fd particles for eliciting and monitoring antigen-specific CTLs.

scholarly journals Anergy in Peripheral Memory Cd4+ T Cells Induced by Low Avidity Engagement of T Cell Receptor

2001 ◽  
Vol 194 (6) ◽  
pp. 719-732 ◽  
Author(s):  
Saied Mirshahidi ◽  
Ching-Tai Huang ◽  
Scheherazade Sadegh-Nasseri
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Critical Role ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Memory Cd4 T Cells

Induction of tolerance in self-reactive memory T cells is an important process in the prevention of autoimmune responses against peripheral self-antigens in autoimmune diseases. Although naive T cells can readily be tolerized, memory T cells are less susceptible to tolerance induction. Recently, we demonstrated that low avidity engagement of T cell receptor (TCR) by low densities of agonist peptides induced anergy in T cell clones. Since memory T cells are more responsive to lower antigenic stimulation, we hypothesized that a low avidity TCR engagement may induce tolerance in memory T cells. We have explored two antigenic systems in two transgenic mouse models, and have tracked specific T cells that are primed and show memory phenotype. We demonstrate that memory CD4+ T cells can be rendered anergic by presentation of low densities of agonist peptide–major histocompatibility complex complexes in vivo. We rule out other commonly accepted mechanisms for induction of T cell tolerance in vivo, such as deletion, ignorance, or immunosuppression. Anergy is the most likely mechanism because addition of interleukin 2–reversed anergy in specific T cells. Moreover, cytotoxic T lymphocyte antigen (CTLA)-4 plays a critical role in the induction of anergy because we observed that there was increased surface expression of CTLA-4 on anergized T cells, and that injection of anti–CTLA-4 blocking antibody restored anergy in vivo.

scholarly journals The Interplay of HIV-1 and Macrophages in Viral Persistence

2021 ◽  
Vol 12 ◽  
Author(s):  
Chynna M. Hendricks ◽  
Thaissa Cordeiro ◽  
Ana Paula Gomes ◽  
Mario Stevenson
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Viral Persistence ◽  
Vital Role ◽  
Highly Active ◽  
Antiretroviral Therapies ◽  
Memory Cd4 T Cells ◽  
Hiv 1

HIV-1 has evolved mechanisms to evade host cell immune responses and persist for lifelong infection. Latent cellular reservoirs are responsible for this persistence of HIV-1 despite the powerful effects of highly active antiretroviral therapies (HAART) to control circulating viral load. While cellular reservoirs have been extensively studied, much of these studies have focused on peripheral blood and resting memory CD4+ T cells containing latent HIV-1 provirus; however, efforts to eradicate cellular reservoirs have been stunted by reservoirs found in tissues compartments that are not easily accessible. These tissues contain resting memory CD4+ T cells and tissue resident macrophages, another latent cellular reservoir to HIV-1. Tissue resident macrophages have been associated with HIV-1 infection since the 1980s, and evidence has continued to grow regarding their role in HIV-1 persistence. Specific biological characteristics play a vital role as to why macrophages are latent cellular reservoirs for HIV-1, and in vitro and in vivo studies exhibit how macrophages contribute to viral persistence in individuals and animals on antiretroviral therapies. In this review, we characterize the role and evolutionary advantages of macrophage reservoirs to HIV-1 and their contribution to HIV-1 persistence. In acknowledging the interplay of HIV-1 and macrophages in the host, we identify reasons why current strategies are incapable of eliminating HIV-1 reservoirs and why efforts must focus on eradicating reservoirs to find a future functional cure.

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 ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Population ◽  
Cd4 T Cells ◽  
Effector Memory ◽  
Healthy Humans ◽  
In Vivo Labeling ◽  
Memory Cd4 T Cells ◽  
Doubling Times

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.

scholarly journals CD25+FoxP3+Memory CD4 T Cells Are Frequent Targets of HIV InfectionIn Vivo

2016 ◽  
Vol 90 (20) ◽  
pp. 8954-8967 ◽  
Author(s):  
Mkunde Chachage ◽  
Georgios Pollakis ◽  
Edmund Osei Kuffour ◽  
Kerstin Haase ◽  
Asli Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Hiv Dna ◽  
Active Viral Replication ◽  
Memory Cd4 T Cells

ABSTRACTInterleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replicationin vitroand facilitates homeostatic proliferation of CD25+FoxP3+CD4+T cells. CD25+FoxP3+CD4+T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25+FoxP3+CD4+T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV+and HIV−study volunteers. Different memory CD4+T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV+subjects, 51% (median) of CD25+FoxP3+CD4+T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67+cells were detected in CD25+FoxP3+memory CD4+T cells (median, 27.6%) in comparison to CD25−FoxP3−memory CD4+T cells (median, 4.1%;P< 0.0001). HIV DNA content was 15-fold higher in CD25+FoxP3+memory CD4+T cells than in CD25−FoxP3−T cells (P= 0.003). EnvV1V3 sequences derived from CD25+FoxP3+memory CD4+T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25+FoxP3+memory CD4+T cells might facilitate efficient HIV infectionin vivoand passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.IMPORTANCEDespite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replicationin vivois incompletely understood.In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25+FoxP3+memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferationin vivo. Our results show that CD25+FoxP3+memory CD4+T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25−FoxP3−memory CD4 T cell subsets. The specific cellular characteristics of CD25+FoxP3+memory CD4+T cells probably facilitate efficient HIV infectionin vivoand passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear.

scholarly journals Basophils Initiate IL-4 Production during a Memory T-dependent Response

2004 ◽  
Vol 200 (7) ◽  
pp. 857-870 ◽  
Author(s):  
Marat V. Khodoun ◽  
Tatyana Orekhova ◽  
Crystal Potter ◽  
Suzanne Morris ◽  
Fred D. Finkelman
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Fluorescent Protein ◽  
Memory T Cells ◽  
Cell Types ◽  
Primary Response ◽  
Capture Assay ◽  
Green Fluorescent ◽  
Memory Cd4 T Cells

Experiments were performed to characterize and identify the cellular sources of the secondary interleukin (IL)-4 response to a T cell–dependent antigen. Mice were primed by immunization with goat anti–mouse immunoglobulin (Ig)D antibody (GaMD), which stimulates naive CD4+ T cells to secrete IL-4 in 3–4 d. When challenged with goat serum 14 d after immunization, GaMD-primed mice generated an IL-4 response that exceeded the primary response by ∼100-fold, started in &lt;2 h, and lasted for 4 d. Studies with 4get mice, in which cells with an accessible Il4 gene express a green fluorescent protein (GFP), revealed CD4+ memory T cells, natural killer T cells, basophils, mast cells, and eosinophils as possible rapid producers of IL-4. GFP+CD4+ T cells and basophils expanded more in the spleen than the other cell types during the primary response to GaMD. Quantitation of in vivo IL-4 production by the in vivo cytokine capture assay after individual cell types were selectively stimulated or deleted demonstrated that basophils and memory CD4+ T cells account for most of the secondary IL-4 response, with basophils initiating that response through IgE/FcεRI-mediated signaling but secreting IL-4 for &lt;4 h and memory T cells secreting IL-4 within 4 h and continuing to secrete this cytokine for 4 d.

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