scholarly journals HIV reservoir size is determined prior to ART initiation and linked to CD8 T cell activation and memory expansion

2019 ◽  
Author(s):  
Genevieve E Martin ◽  
Matthew Pace ◽  
Freya Shearer ◽  
Eva Zilber ◽  
Jacob Hurst ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Art Initiation ◽  
One Year

AbstractInitiation of antiretroviral therapy (ART) in early compared with chronic HIV infection is associated with a smaller HIV reservoir. This longitudinal analysis of 63 individuals who commenced ART during primary HIV infection (PHI) investigates which pre-and post-therapy factors associate most closely with reservoir size (HIV DNA) following treatment initiation during PHI. The best predictor of reservoir size at one-year was pre-ART HIV DNA which was in turn significantly associated with CD8 memory differentiation (effector memory, naïve and T-betnegEomesnegsubsets), CD8 T cell activation (CD38 expression) and PD-1 and Tim-3 expression on memory CD4 T cells. No associations were found for any immunological variables following one-year of ART. HIV reservoir size is determined around the time of ART initiation in individuals treated during PHI. CD8 T cell activation and memory expansion are linked to HIV reservoir size, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

scholarly journals Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion

2019 ◽  
Vol 221 (7) ◽  
pp. 1135-1145 ◽  
Author(s):  
Genevieve E Martin ◽  
Matthew Pace ◽  
Freya M Shearer ◽  
Eva Zilber ◽  
Jacob Hurst ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Hiv Dna ◽  
Art Initiation ◽  
Immunodeficiency Virus

Abstract Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet−Eomes− subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

The Dominant Source of CD4+ and CD8+ T-Cell Activation in HIV Infection Is Antigenic Stimulation

2000 ◽  
Vol 25 (3) ◽  
pp. 203-211 ◽  
Author(s):  
James W. T Cohen Stuart ◽  
Mette D Hazebergh ◽  
Dörte Hamann ◽  
Sigrid A Otto ◽  
Jan C. C Borleffs ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Antigenic Stimulation ◽  
Dominant Source

scholarly journals CD4+ and CD8+ T Cell Activation Are Associated with HIV DNA in Resting CD4+ T Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110731 ◽  
Author(s):  
Leslie R. Cockerham ◽  
Janet D. Siliciano ◽  
Elizabeth Sinclair ◽  
Una O'Doherty ◽  
Sarah Palmer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Hiv Dna

scholarly journals Interferon-Alpha Administration Enhances CD8+ T Cell Activation in HIV Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30306 ◽  
Author(s):  
Maura Manion ◽  
Benigno Rodriguez ◽  
Kathleen Medvik ◽  
Gareth Hardy ◽  
Clifford V. Harding ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Interferon Alpha ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell

scholarly journals Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Genevieve E. Martin ◽  
Debattama R. Sen ◽  
Matthew Pace ◽  
Nicola Robinson ◽  
Jodi Meyerowitz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cell Dysfunction ◽  
Art Initiation ◽  
T Cell Dysfunction ◽  
Checkpoint Receptors

T cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated from early PHI with up to three years of ART. Compared with HIV-uninfected controls, CD4 and CD8 T cells from early HIV infection were characterised by T cell activation and increased expression of the immune checkpoint receptors (ICRs) PD1, Tim-3 and TIGIT. Three years of ART lead to partial – but not complete – normalisation of ICR expression, the dynamics of which varied for individual ICRs. For HIV-specific cells, epigenetic profiling of tetramer-sorted CD8 T cells revealed that epigenetic features of exhaustion typically seen in chronic HIV infection were already present early in PHI, and that ART initiation during PHI resulted in only a partial shift of the epigenome to one with more favourable memory characteristics. These findings suggest that although ART initiation during PHI results in significant immune reconstitution, there may be only partial resolution of HIV-related phenotypic and epigenetic changes.

scholarly journals Thymoproteasome-Expressing Mesenchymal Stromal Cells Confer Protective Anti-Tumor Immunity via Cross-Priming of Endogenous Dendritic Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Jean-Pierre Bikorimana ◽  
Nehme El-Hachem ◽  
Abed El-Hakim El-Kadiry ◽  
Jamilah Abusarah ◽  
Natasha Salame ◽  
...  
Keyword(s):  
T Cell ◽  
Mesenchymal Stromal Cells ◽  
T Cell Activation ◽  
Stromal Cells ◽  
Cell Activation ◽  
De Novo ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Phagocytic Cells ◽  
Cell Immunity

Proteasomes are complex macromolecular structures existing in various forms to regulate a myriad of cellular processes. Besides degrading unwanted or misfolded proteins (proteostasis), distinct immune functions were ascribed for the immunoproteasome and thymoproteasome (TPr) complexes. For instance, antigen degradation during ongoing immune responses mainly relies on immunoproteasome activity, whereas intrathymic CD8 T-cell development requires peptide generation by the TPr complex. Despite these substantial differences, the functional contribution of the TPr to peripheral T-cell immunity remains ill-defined. We herein explored whether the use of mesenchymal stromal cells (MSCs) engineered to exhibit altered proteasomal activity through de novo expression of the TPr complex can be exploited as a novel anti-cancer vaccine capable of triggering potent CD8 T-cell activation. Phenotypic and molecular characterization of MSC-TPr revealed a substantial decrease in MHCI (H2-Kb and H2-Dd) expression along with elevated secretion of various chemokines (CCL2, CCL9, CXCL1, LIX, and CX3CL1). In parallel, transcriptomic analysis pinpointed the limited ability of MSC-TPr to present endogenous antigens, which is consistent with their low expression levels of the peptide-loading proteins TAP, CALR, and PDAI3. Nevertheless, MSC-TPr cross-presented peptides derived from captured soluble proteins. When tested for their protective capacity, MSC-TPr triggered modest anti-tumoral responses despite efficient generation of effector memory CD4 and CD8 T cells. In contrast, clodronate administration prior to vaccination dramatically enhanced the MSC-TPr-induced anti-tumoral immunity clearly highlighting a refractory role mediated by phagocytic cells. Thus, our data elute to a DC cross-priming-dependant pathway in mediating the therapeutic effect of MSC-TPr.

Interleukin-21 Plays an Important Role in CD8 T-Cell Activation and Poor Outcome in HIV Infection

2013 ◽  
Vol 33 (3) ◽  
pp. 115-120 ◽  
Author(s):  
Hua-Ying Zhou ◽  
Yu-Huang Zheng ◽  
Yan He ◽  
Zi Chen ◽  
Mei He ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Poor Outcome ◽  
Interleukin 21

scholarly journals Antiretroviral Therapy Initiated Within 6 Months of HIV Infection Is Associated With Lower T-Cell Activation and Smaller HIV Reservoir Size

2013 ◽  
Vol 208 (8) ◽  
pp. 1202-1211 ◽  
Author(s):  
Vivek Jain ◽  
Wendy Hartogensis ◽  
Peter Bacchetti ◽  
Peter W. Hunt ◽  
Hiroyu Hatano ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hiv Reservoir

Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 942-947 ◽  
Author(s):  
Steven G. Deeks ◽  
Christina M. R. Kitchen ◽  
Lea Liu ◽  
Hua Guo ◽  
Ron Gascon ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Hiv Disease ◽  
Set Point ◽  
Hiv Rna ◽  
Cell Changes ◽  
Untreated Individuals

AbstractAlthough generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation “set point” is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4+ and CD8+ T cells was measured longitudinally in 68 antiretroviral-untreated individuals and 83 antiretroviral-treated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8+ T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10 000 copies/mL. Among untreated patients, the level of CD8+ T-cell activation varied widely among individuals but often remained stable within a given individual. CD8+ T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4+ T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4+ T cells are lost over time.

scholarly journals Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point

Immunity ◽  
2015 ◽  
Vol 43 (3) ◽  
pp. 591-604 ◽  
Author(s):  
Zaza M. Ndhlovu ◽  
Philomena Kamya ◽  
Nikoshia Mewalal ◽  
Henrik N. Kløverpris ◽  
Thandeka Nkosi ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Set Point ◽  
Kinetics Of
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