Flow cytometric analysis of the stimulatory response of T cell subsets from normal and HIV-1+ individuals to various mitogenic stimuli <i>in vitro</i>

Medina, Eva; Borthwick, Nicola; Johnson, M. D.; Miller, S D; Bofill, Margarita

doi:10.1111/j.1365-2249.1994.tb06079.x

Cited by 16 publications

(3 citation statements)

References 26 publications

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“…To further characterize the effects of 3-OH-CB28 on proliferating T cells, we stimulated PBMCs with tetanus toxoid (TT) or cytomegalovirus (CMV) antigens as well as with non-specific mitogen phytohemagglutinin (PHA) (Ullman et al 1990; Medina et al 1994). As the TT used in this study is a single antigen, whereas the CMV proteins contain multiple antigens, a higher frequency of responding T cells in CMV- versus TT-cultured PBMCs could be expected.…”

Section: Resultsmentioning

confidence: 99%

Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure

et al. 2016

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Polychlorinated biphenyls (PCBs) are organochlorine pollutants with a worldwide dissemination. We examined telomere length (TL) in peripheral blood cells of 207 individuals with a high body burden of PCBs due to occupational exposure in a transformer recycling company. Whereas TL in granulocytes was not affected, the age-adjusted TL in lymphocytes (∆TLLymph) of exposed individuals was significantly shorter than expected [−0.77 kb; 95 % confidence interval (CI) −0.9316; −0.6052; p = 0.0001]. PCB exposure did not affect lymphocyte numbers or T cell receptor excision circle (TREC) levels in T cells, suggesting that PCBs cause loss of telomeric DNA in T cells due to their metabolic activation and antigen-stimulated proliferation. In support of this hypothesis, blood plasma levels of PCB-exposed individuals inhibited expression of telomerase, the telomere elongating enzyme in vitro in antigen-specific T cell proliferation assays. 3-OH-CB28, a downstream metabolite of the lower chlorinated PCB-28 in PCB-exposed individuals (mean blood plasma concentration: 0.185 ± 0.68 ng/mL), inhibited telomerase gene expression within 48 h of incubation in lymphoproliferative assays starting at a concentration of 0.27–6.75 µg/mL and accelerated telomere shortening in long-term cell culture experiments. Accelerated telomere shortening due to PCB exposure may lead to limitations of cell renewal and clonal expansion of lymphocyte populations. As PCB-related immune dysfunctions have been linked to increased susceptibility to infectious diseases and increased risk of cancer, our data provide a possible explanation, for how PCBs could promote infections and cancer through limiting immune surveillance.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1725-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure

et al. 2016

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“…2). However, mitogenic stimulation with phytohemagglutinin (PHA) selectively promoted higher proliferation and greater calcium flux in the naive T cell subset, diminishing the differences between memory and naive T cells in supporting HIV replication (8,9,55). In our system, cells were only stimulated with the CD3/CD28 beads after infection to give a similar activation background for the virus to replicate.…”

Section: Discussionmentioning

confidence: 99%

A Dichotomy in Cortical Actin and Chemotactic Actin Activity between Human Memory and Naive T Cells Contributes to Their Differential Susceptibility to HIV-1 Infection

Wang

Guo

et al. 2012

Journal of Biological Chemistry

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Human memory and naive CD4 T cells can mainly be identified by the reciprocal expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO memory CD4 T cells are preferentially infected and serve as a major viral reservoir. The molecular mechanism dictating this differential susceptibility to HIV-1 remains largely obscure. Here, we report that the different susceptibility of memory and naive T cells to HIV is not determined by restriction factors such as Apobec3G or BST2. However, we observed a phenotypic distinction between human CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be distinguished as CD45RO+Actinhigh. In contrast, CD45RA T cells are phenotypically CD45RA+Actinlow. In addition, the cortical actin in CD45RO memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic induction by SDF-1, whereas that of naive cells cannot, despite a similar level of the chemokine receptor CXCR4 present on both cells. We further demonstrate that this difference in the cortical actin contributes to their differential susceptibility to HIV-1; resting memory but not naive T cells are highly responsive to HIV-mediated actin dynamics that promote higher levels of viral entry and early DNA synthesis in resting memory CD4 T cells. Furthermore, transient induction of actin dynamics in resting naive T cells rescues HIV latent infection following CD3/CD28 stimulation. These results suggest a key role of chemotactic actin activity in facilitating HIV-1 latent infection of these T cell subsets.

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“…After 18 h incubation, cells in the lower chamber were harvested, washed, counted and resuspended at 10 6 /ml in RPMI‐1640 medium without IL‐2. The numbers of viable cells were determined daily by counting on a flow cytometer using the forward scatter (FSC) and side scatter (SSC) profiles to identify viable cells [11]. The data are given as the percentage recovery of viable cells expressed as a percentage of the initial input, thus low cell recovery reflects poor survival and high cell death.…”

Section: Methodsmentioning

confidence: 99%

Transendothelial migration confers a survival advantage to activated T lymphocytes: role of LFA-1/ICAM-1 interactions

Borthwick

Akbar

Buckley

et al. 2003

Clinical and Experimental Immunology

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SUMMARYThe clearance of activated T lymphocytes by apoptosis is an essential component in the resolution of the immune response; however, certain signals received within inflamed tissue may result in the persistence of activated T cells. Our previous work has shown that, when compared with resting cells, effector cells migrate more efficiently across endothelium, thus such cells may be selectively recruited to sites of inflammation. We hypothesized that transmigration of T cells across endothelium might influence cell survival. We have generated T cell lines by culturing in IL-2 following PHA activation. These T cell lines die rapidly by apoptosis when deprived of IL-2 (53·7 ± 4·0% survival after 24 h). In contrast, cells that have migrated across human umbilical vein endothelial cells (HUVEC) survived significantly better than control cells (80·3 ± 3·6%, n = 18, P < 0·001). Endothelial cell conditioned medium was also able to reduce apoptosis, but this effect was small when compared with the protective effect of transmigration. Culture of T lymphocytes on fibronectin, or RGD peptides, or in suspension with a range of chemokines active on T cells, including RANTES and lymphotactin had no effect on survival. In contrast, blocking LFA-l/ICAM-l interactions reduced the protective effect of transmigration (42·3 ± 6·7% reduction). Culture of activated T cells on immobilized ICAM-l alone also increased survival. These results indicate that signals received by activated T cells during extravasation can influence their subsequent survival within tissue, and implicates the involvement of LF A-l/ICAM-l interactions.

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Flow cytometric analysis of the stimulatory response of T cell subsets from normal and HIV-1+ individuals to various mitogenic stimuli in vitro

Cited by 16 publications

References 26 publications

Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure

Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure

A Dichotomy in Cortical Actin and Chemotactic Actin Activity between Human Memory and Naive T Cells Contributes to Their Differential Susceptibility to HIV-1 Infection

Transendothelial migration confers a survival advantage to activated T lymphocytes: role of LFA-1/ICAM-1 interactions

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