scholarly journals CD38 expression on CD8 T cells has a weak association with CD4 T-cell recovery and is a poor marker of viral replication in HIV-1-infected patients on antiretroviral therapy

HIV Medicine ◽  
2008 ◽  
Vol 9 (2) ◽  
pp. 118-125 ◽  
Author(s):  
A Steel ◽  
L John ◽  
MH Shamji ◽  
DC Henderson ◽  
FM Gotch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Cell Recovery ◽  
Cd38 Expression ◽  
Weak Association ◽  
Hiv 1

scholarly journals Reconstitution of Peripheral T Cells by Tissue-Derived CCR4+ Central Memory Cells Following HIV-1 Antiretroviral Therapy

2016 ◽  
Vol 1 (2) ◽  
pp. 260 ◽  
Author(s):  
Yolanda D. Mahnke ◽  
Kipper Fletez-Brant ◽  
Irini Sereti ◽  
Mario Roederer
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Plasma Viral Load ◽  
Cd4 T Cell ◽  
Cell Numbers ◽  
Cell Counts ◽  
Hiv 1

Background. Highly active antiretroviral therapy induces clinical benefits to HIV-1 infected individuals, which can be striking in those with progressive disease. Improved survival and decreased incidence of opportunistic infections go hand in hand with a suppression of the plasma viral load, an increase in peripheral CD4+ T-cell counts, as well as a reduction in the activation status of both CD4+ and CD8+ T cells.Methods. We investigated T-cell dynamics during ART by polychromatic flow cytometry in total as well as in HIV-1-specific CD4+ and CD8+ T cells. We also measured gene expression by single cell transcriptomics to assess functional state.Results. The cytokine pattern of HIV-specific CD8+ T cells was not altered after ART, though their magnitude decreased significantly as the plasma viral load was suppressed to undetectable levels. Importantly, while CD4+ T cell numbers increased substantially during the first year, the population did not normalize: the increases were largely due to expansion of mucosal-derived CCR4+ CD4+ TCM; transcriptomic analysis revealed that these are not classical Th2-type cells.Conclusion. The apparent long-term normalization of CD4+ T-cell numbers following ART does not comprise a normal balance of functionally distinct cells, but results in a dramatic Th2 shift of the reconstituting immune system.

scholarly journals Prolonged Antiretroviral Therapy Preserves HIV-1-Specific CD8 T Cells with Stem Cell-Like Properties

2015 ◽  
Vol 89 (15) ◽  
pp. 7829-7840 ◽  
Author(s):  
Selena Vigano ◽  
Jordi Negron ◽  
Zhengyu Ouyang ◽  
Eric S. Rosenberg ◽  
Bruce D. Walker ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Cellular Immune ◽  
Hiv 1

ABSTRACTHIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-specific CD8 T cells with stem cell-like properties, termed T memory stem cells (TSCMcells), is enriched in patients receiving suppressive antiretroviral therapy compared with their levels in untreated progressors or controllers. In addition, a prolonged duration of antiretroviral therapy was associated with a progressive increase in the relative proportions of these stem cell-like HIV-1-specific CD8 T cells. Interestingly, the proportions of HIV-1-specific CD8 TSCMcells and total HIV-1-specific CD8 TSCMcells were associated with the CD4 T cell counts during treatment with antiretroviral therapy but not with CD4 T cell counts, viral loads, or immune activation parameters in untreated patients, including controllers. HIV-1-specific CD8 TSCMcells had increased abilities to secrete interleukin-2 in response to viral antigen, while secretion of gamma interferon (IFN-γ) was more limited in comparison to alternative HIV-1-specific CD8 T cell subsets; however, only proportions of IFN-γ-secreting HIV-1-specific CD8 TSCMcells were associated with CD4 T cell counts during antiretroviral therapy. Together, these data suggest that HIV-1-specific CD8 TSCMcells represent a long-lasting component of the cellular immune response to HIV-1 that persists in an antigen-independent fashion during antiretroviral therapy but seems unable to survive and expand under conditions of ongoing viral replication during untreated infection.IMPORTANCEMemory CD8 T cells that imitate the functional properties of stem cells to maintain lifelong cellular immunity have been hypothesized for many years, but only recently have such cells, termed T memory stem cells (TSCMcells), been physically identified and isolated in humans, mice, and nonhuman primates. Here, we investigated whether cellular immune responses against HIV-1 include such T memory stem cells. Our data show that HIV-1-specific CD8 T memory stem cells are detectable during all stages of HIV-1 infection but occur most visibly at times of prolonged viral antigen suppression by antiretroviral combination therapy. These cells may therefore be particularly relevant for designing antiviral immune defense strategies against the residual reservoir of HIV-1-infected cells that persists despite treatment and leads to viral rebound upon treatment discontinuation.

scholarly journals Higher CD27+CD8+ T Cells Percentages during Suppressive Antiretroviral Therapy Predict Greater Subsequent CD4+ T Cell Recovery in Treated HIV Infection

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84091 ◽  
Author(s):  
Lillian Seu ◽  
Gabriel M. Ortiz ◽  
Lorrie Epling ◽  
Elizabeth Sinclair ◽  
Louise A. Swainson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Cell Recovery

scholarly journals Longitudinal Changes in Cd4+, Cd8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis

2019 ◽  
Vol 5 (3) ◽  
pp. 63
Author(s):  
Alice Bayiyana ◽  
Samuel Okurut ◽  
Rose Nabatanzi ◽  
Godfrey Zziwa ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Cryptococcal Meningitis ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Memory Subset

Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.

scholarly journals Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

1999 ◽  
Vol 96 (26) ◽  
pp. 15167-15172 ◽  
Author(s):  
N. M. Ferguson ◽  
F. deWolf ◽  
A. C. Ghani ◽  
C. Fraser ◽  
C. A. Donnelly ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Highly Active ◽  
Hiv 1

scholarly journals HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

2019 ◽  
Vol 219 (12) ◽  
pp. 1948-1958 ◽  
Author(s):  
Christine Kelly ◽  
Henry C Mwandumba ◽  
Robert S Heyderman ◽  
Kondwani Jambo ◽  
Raphael Kamng’ona ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Arterial Stiffness ◽  
Cell Count ◽  
Cd8 T Cells ◽  
Sub Saharan Africa ◽  
Cd4 T Cell ◽  
Sub Saharan ◽  
Cd4 T Cell Count

Abstract Background The contribution of immune activation to arterial stiffness and its reversibility in human immunodeficiency virus (HIV)–infected adults in sub-Saharan Africa is unknown. Methods HIV-uninfected and HIV-infected Malawian adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count of <100 cells/μL were enrolled and followed for 44 weeks; enrollment of infected adults occurred 2 weeks after ART initiation. We evaluated the relationship between carotid femoral pulse wave velocity (cfPWV) and T-cell activation (defined as HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence (defined as CD57+ T cells) and monocyte subsets, using normal regression. Results In 279 HIV-infected and 110 HIV-uninfected adults, 142 (37%) had hypertension. HIV was independently associated with a 12% higher cfPWV (P = .02) at baseline and a 14% higher cfPWV at week 10 (P = .02), but the increases resolved by week 22. CD4+ and CD8+ T-cell exhaustion were independently associated with a higher cfPWV at baseline (P = .02). At 44 weeks, arterial stiffness improved more in those with greater decreases in the percentage of CD8+ T cells and the percentage of PD-1+CD8+ T cells (P = .01 and P = .03, respectively). When considering HIV-infected participants alone, the adjusted arterial stiffness at week 44 tended to be lower in those with higher baseline percentage of PD-1+CD8+ T cells (P = .054). Conclusions PD-1+CD8+ T-cells are associated with HIV-related arterial stiffness, which remains elevated during the first 3 months of ART. Resources to prevent cardiovascular disease in sub-Saharan Africa should focus on blood pressure reduction and individuals with a low CD4+ T-cell count during early ART.

scholarly journals 739 Intratumor childhood vaccine-specific CD4+ T cell recall helps antitumor CD8 T cells

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A770-A770
Author(s):  
Michael Brown ◽  
Zachary McKay ◽  
Yuanfan Yang ◽  
Darell Bigner ◽  
Smita Nair ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Replication ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Antitumor Efficacy ◽  
Polio Vaccine ◽  
Recall Antigen ◽  
Childhood Vaccine

BackgroundPVSRIPO, a recombinant poliovirus derived from the live-attenuated Sabin oral polio vaccine strain, is being tested in multi-institutional phase II clinical trials for recurrent glioblastoma (NCT04479241) and unresectable, PD-1 refractory melanoma (NCT04577807) in combination with PD1 blockade. PVSRIPO capsid is identical to the Sabin vaccine strain and >99% identical to the inactivated Polio vaccine (IPOL, Salk), against which public health mandated childhood vaccination is near universal. In non-vaccinated mice, PVSRIPO mediates antitumor efficacy in a replication-dependent manner via engaging innate inflammation and antitumor T cells. Accordingly, it is anticipated that pre-existing immunity to PVSRIPO impedes antitumor therapy. However, recent evidence indicates that immunological 'recall', or reactivation of memory T cells, may mediate anti-tumor effects.MethodsThe impact of prior polio vs control (KLH) vaccination on intratumor viral replication, tumor inflammation, and overall tumor growth after intratumor PVSRIPO therapy was assessed in murine tumor models. The role of polio capsid and tetanus recall antigens in mediating intratumor inflammation and antitumor efficacy was similarly studied in mice non-permissive to PVSRIPO infection. To mechanistically define antitumor effects of polio recall, B cell and CD8 T cell knockout mice were used, in addition to adoptive transfer of CD4+ T cells from vaccinated mice. Intratumor polio or tetanus recall antigen therapy was performed after OT-I transfer (OVA-specific T cells) in the B16-OVA melanoma model to gauge antitumor T cell activity. Lastly, the inflammatory effects of polio and tetanus antigens was tested in human peripheral blood mononuclear cells (PBMCs).ResultsDespite curtailing intratumor viral replication, prior polio vaccination in mice potentiated subsequent antitumor efficacy of PVSRIPO. Intratumor recall responses induced by polio and tetanus antigens also delayed tumor growth. Recall antigen therapy was associated with marked intratumor influx of eosinophils, conventional CD4+ T cells, and increased expression of IFN-g, TNF, and Granzyme B in tumor infiltrating T cells. The antitumor efficacy of polio recall antigen was mediated by CD4+ T cells, partially depended upon CD8+ T cells, and was impaired by B cells. Both polio and tetanus recall antigen therapy bolstered the antitumor function of tumor-specific OT-I CD8+ T cells. Polio and tetanus antigens induced CXCL10 and type I/II/III IFNs in PBMCs in vitro.ConclusionsChildhood vaccine-specific CD4+ T cells hold cancer immunotherapy potential. In the context of PVSRIPO therapy, antitumor and inflammatory effects of polio vaccine-specific CD4+ T cell recall supersedes inhibitory effects of attenuated intratumor viral replication, and represents a novel mechanism of action.Ethics ApprovalThe animal work described in this study was approved by the Duke University IACUC.

scholarly journals Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

2008 ◽  
Vol 205 (12) ◽  
pp. 2763-2779 ◽  
Author(s):  
R. Brad Jones ◽  
Lishomwa C. Ndhlovu ◽  
Jason D. Barbour ◽  
Prameet M. Sheth ◽  
Aashish R. Jha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Surface Expression ◽  
Cell Dysfunction ◽  
Cd38 Expression ◽  
Immunodeficiency Virus ◽  
T Cell Dysfunction ◽  
Novel Target ◽  
Hiv 1

Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1–infected individuals to a mean of 49.4 ± SD 12.9% of CD8+ T cells expressing Tim-3 in HIV-1–infected chronic progressors versus 28.5 ± 6.8% in HIV-1–uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1–infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1–specific CD8+ T cells. Tim-3–expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1–specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1–associated T cell dysfunction.

Sign in / Sign up

Export Citation Format

Share Document