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

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.

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

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz015 ◽

2019 ◽

Vol 219 (12) ◽

pp. 1948-1958 ◽

Cited By ~ 1

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.

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CD8 T cells targeting adapted epitopes in chronic HIV infection promote dendritic cell maturation and CD4 T cell trans-infection

PLoS Pathogens ◽

10.1371/journal.ppat.1007970 ◽

2019 ◽

Vol 15 (8) ◽

pp. e1007970 ◽

Cited By ~ 5

Author(s):

Kai Qin ◽

Sushma Boppana ◽

Victor Y. Du ◽

Jonathan M. Carlson ◽

Ling Yue ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Dendritic Cell ◽

Hiv Infection ◽

Cd8 T Cells ◽

Dendritic Cell Maturation ◽

Cd4 T Cell ◽

Cell Maturation ◽

Trans Infection ◽

Chronic Hiv Infection

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Robust CD4+ T-cell recovery in adults transplanted with cord blood and no antithymocyte globulin

Blood Advances ◽

10.1182/bloodadvances.2019000836 ◽

2020 ◽

Vol 4 (1) ◽

pp. 191-202 ◽

Cited By ~ 7

Author(s):

Ioannis Politikos ◽

Jessica A. Lavery ◽

Patrick Hilden ◽

Christina Cho ◽

Taylor Borrill ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cord Blood ◽

Cd8 T Cells ◽

Antithymocyte Globulin ◽

Cd8 T Cell ◽

T Cell Subsets ◽

Cd4 T Cell ◽

Cell Recovery ◽

Cell Counts

Abstract Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+ T cells was faster than CD8+ T cells with median CD4+ T-cell counts exceeding 200/mm3 at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+ subsets, whereas effector and EM were the most common CD8+ T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+ cell dose was associated with improved CD4+ and CD4+CD45RA+ T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+ T cells, but lower CD4+ T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+ T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+ T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3 and 150/mm3 by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+ T-cell recovery, and CD4+ recovery reduced mortality risk.

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Effects of HCV co-infection on apoptosis of CD4+ T-cells in HIV-positive patients

Clinical Science ◽

10.1042/cs20080532 ◽

2009 ◽

Vol 116 (12) ◽

pp. 861-870 ◽

Cited By ~ 29

Author(s):

Christian Körner ◽

Benjamin Krämer ◽

Daniela Schulte ◽

Martin Coenen ◽

Stefan Mauss ◽

...

Keyword(s):

T Cells ◽

Hepatitis C ◽

T Cell ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Cell Apoptosis ◽

Cd4 T Cells ◽

Cd4 T Cell ◽

Hiv Positive ◽

T Cell Apoptosis

Apoptosis importantly contributes to loss of CD4+ T-cells in HIV infection, and modification of their apoptosis may explain why HIV/HCV (hepatitis C virus)-co-infected patients are more likely to die from liver-related causes, although the effects of HCV on HIV infection remain unclear. In the present study, we studied in a cross-sectional and serial analysis spontaneous ex vivo CD4+ T-cell apoptosis in HIV/HCV-co-infected and HIV-mono-infected patients before and after HAART (highly active antiretroviral therapy). Apoptosis of peripheral blood CD4+ T-cells was measured by both a PARP [poly(ADP-ribose) polymerase] and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay to detect cells with irreversible apoptosis. Although hepatitis C alone did not increase CD4+ T-cell apoptosis, HCV co-infection disproportionately increased elevated rates of apoptosis in CD4+ T-cells from untreated HIV-positive patients. Increased CD4+ T-cell apoptosis was closely correlated with HIV, but not HCV, viral loads. Under HAART, increased rates of CD4+ T-cell apoptosis rapidly decreased both in HIV-mono-infected and HIV/HCV-co-infected patients, without any significant difference in apoptosis rates between the two patient groups after 4 weeks of therapy. Nevertheless residual CD4+ T-cell apoptosis did not reach the normal levels seen in healthy controls and remained higher in HIV patients receiving protease inhibitors than in patients with other antiretroviral regimens. The results of the present study suggest that HCV co-infection sensitizes CD4+ T-cells towards apoptosis in untreated HIV-positive patients. However, this effect is rapidly lost under effective antiretroviral therapy.

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

Pathogens and Immunity ◽

10.20411/pai.v1i2.129 ◽

2016 ◽

Vol 1 (2) ◽

pp. 260 ◽

Cited By ~ 8

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.

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

Journal of Virology ◽

10.1128/jvi.00789-15 ◽

2015 ◽

Vol 89 (15) ◽

pp. 7829-7840 ◽

Cited By ~ 24

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.

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The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial

Blood ◽

10.1182/blood-2012-06-436345 ◽

2013 ◽

Vol 121 (23) ◽

pp. 4635-4646 ◽

Cited By ~ 94

Author(s):

Peter W. Hunt ◽

Nancy S. Shulman ◽

Timothy L. Hayes ◽

Viktor Dahl ◽

Ma Somsouk ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

T Cell Activation ◽

Cd8 T Cells ◽

Peripheral Blood ◽

Cell Activation ◽

Rectal Mucosa ◽

Cd4 T Cell ◽

Cell Recovery ◽

Key Points

Key Points Maraviroc intensification unexpectedly increases T-cell activation in peripheral blood and rectal mucosa during treated HIV infection. Maraviroc appears to redistribute CD8+ T cells from the gut to peripheral blood during treated HIV infection.

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Kinetics of CD4+ T-cell recovery amongst HIV load suppressed patients on first-line antiretroviral therapy in Yaoundé, Cameroon

International Journal of Biological and Chemical Sciences ◽

10.4314/ijbcs.v15i3.3 ◽

2021 ◽

Vol 15 (3) ◽

pp. 881-888

Author(s):

Cedric Happi Mbakam ◽

Julius Mbekem Nwobegahay ◽

Cybelle Fodieu Mezajou ◽

Franklin Agueguia Azebaze ◽

Leopold Mbous Nguimbus ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Antiretroviral Therapy ◽

Cd4 T Cells ◽

Standard Form ◽

University Teaching ◽

Cd4 T Cell ◽

Cell Recovery ◽

First Line ◽

Kinetics Of

HIV infected patients on Antiretroviral Therapy (ART) are exposed to various immunological disorders. Immune reconstitution is one of the most challenging problem linked to morbidity and mortality in HIV patients. This study aimed at evaluating the kinetics of CD4+ T-cell recovery amongst HIV load suppressed patients on first-line ART in Yaoundé, Cameroon. This was a retrospective cohort study performed at the care and treatment units of the Yaoundé University Teaching Hospital and Essos Hospital Center, with viral suppressed patients initiated on ART between March and July 2015. Data were collected using a standard form and analyzed using R.3.6.2 software. A p<0.05 was considered statistically significant for a 95%CI. Of the 499 viral suppressed participants, 32% (n=160) were male and 68% (n=339) female; 33% and 40% had severe and moderate immunodepression at baseline, respectively; 9% and 28% remain respectively on the same immunological state. CD4+ T-cell count increased by 73%, 49% and 29% for patients that started treatment, with CD4+ <150 cells/ml, 150<CD4+<350 cells/ml and 350<CD4+<500 cells/ml, respectively and 14%, 34% and 40% reached a target of 500 cells/ml or more after 4 years of treatment. Elder patients and males were likely to have CD4+ T-cells less than 350 Cells/ml. Approximately 35% of patient started treatment with CD4+ T-cells <350 Cells/ml. CD4+ T-cells increased significantly during 4 years of treatment but, just 29% in average achieved CD4+ ≥ 500 cells/ml. CD4 T-cells recovery represent and important challenge in the immunological monitoring of long-term HIV infected patients on ART.

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