The effect of androgen deprivation therapy on CD4/CD8 T cells in HIV-negative patients receiving definitive 3D radiation treatment for their prostate carcinoma: Final report of a prospective study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11056-11056
Author(s):  
M. A. Elshaikh ◽  
Z. Abdel Hafeez ◽  
M. Lu ◽  
D. Ibrahim ◽  
T. El Masry ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Radiation Treatment ◽  
Cd8 T Cell ◽  
Total Testosterone ◽  
Blood Samples ◽  
Testosterone Levels ◽  
Cell Counts ◽  
Hiv Negative

11056 Background: CD4 and CD8 T cells play critical roles in human immunity. The aim of this prospective study is to explore the correlation of the absolute CD4/CD8 T cell counts and total testosterone in patients receiving androgen deprivation therapy (ADT) with goserelin acetate and definitive radiation treatment (RT) for their prostate cancer. Methods: Thirty-four HIV-negative patients were included in this study between June 2006 and January 2007. All patients had a baseline total testosterone level (T), PSA, CD4 and CD8 T cell counts. CD4/8 T cells count was measured using flow cytometry. All patients received 6 months of ADT prior to (baseline) and during RT to the prostate. Subsequent blood samples were taken at 2, 8, 12 and 24 months. Blood samples were taken between 8–10 am to control for diurnal variations in CD4/CD8 T cell counts and T levels. To study the correlation of T with CD4/8 T cell changes, the Spearman correlation coefficient was calculated. The study was approved by the appropriate Ethics Committee. Results: Median age for the study patients was 68 years. At baseline, median testosterone level was 350 ng/dL, median CD4 T cell count was 1055 mm3, and median CD8 T cell count was 644 mm3. None of the patients received anti-androgens. At two months, testosterone was at the castrate and subnormal levels in 85% and 100% of the patients, respectively. The lower testosterone levels resulted in significant reduction of CD4 and CD8 T cell counts at 2, 8, 12 and 24 months compared to baseline counts. This effect was more pronounced for CD4 T cells at all time points (p=<0.02). At 24 months, when total testosterone levels were increasing, CD4 and CD8 T cell counts were also following these upward trends. The seen correlation between lower testosterone and decline in CD4 and CD8 T cells was only statistically significant in older patients (>65 years) and was not associated with significant decline in total white blood cell counts. Conclusions: CD4/CD8 T cell counts are sensitive to changes in total testosterone levels. Lower testosterone levels negatively affecting CD4/CD8 T cells counts at all study time points. Since CD4/CD8 T cells play major roles in cellular immunity, further studies are warranted No significant financial relationships to disclose.

scholarly journals Cortisol and epinephrine control opposing circadian rhythms in T cell subsets

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5134-5143 ◽  
Author(s):  
Stoyan Dimitrov ◽  
Christian Benedict ◽  
Dennis Heutling ◽  
Jürgen Westermann ◽  
Jan Born ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Circadian Rhythms ◽  
Cd8 T Cells ◽  
Low Dose ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract Pronounced circadian rhythms in numbers of circulating T cells reflect a systemic control of adaptive immunity whose mechanisms are obscure. Here, we show that circadian variations in T cell subpopulations in human blood are differentially regulated via release of cortisol and catecholamines. Within the CD4+ and CD8+ T cell subsets, naive cells show pronounced circadian rhythms with a daytime nadir, whereas (terminally differentiated) effector CD8+ T cell counts peak during daytime. Naive T cells were negatively correlated with cortisol rhythms, decreased after low-dose cortisol infusion, and showed highest expression of CXCR4, which was up-regulated by cortisol. Effector CD8+ T cells were positively correlated with epinephrine rhythms, increased after low-dose epinephrine infusion, and showed highest expression of β-adrenergic and fractalkine receptors (CX3CR1). Daytime increases in cortisol via CXCR4 probably act to redistribute naive T cells to bone marrow, whereas daytime increases in catecholamines via β-adrenoceptors and, possibly, a suppression of fractalkine signaling promote mobilization of effector CD8+ T cells from the marginal pool. Thus, activation of the major stress hormones during daytime favor immediate effector defense but diminish capabilities for initiating adaptive immune responses.

T Cell Responses during Long-Term Continuous Infusion of MT103 (MEDI-538; Anti-CD19 BiTE) in Patients with Relapsed B-NHL: Data from Dose-Escalation Study MT103-104.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2725-2725 ◽  
Author(s):  
Matthias Klinger ◽  
Peter Kufer ◽  
Petra Kirchinger ◽  
Ralf Lutterbüse ◽  
Eugen Leo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Dose Escalation ◽  
Cell Expansion ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Cell Counts ◽  
T Cell Expansion

Abstract MT103 (MEDI-538) is a bispecific single-chain antibody construct directed at CD3 on human T cells and CD19 on human B lymphoma and normal B cells. Transient linkage of B and T cells by MT103 provides T cells with a T cell receptor (TCR)-like signal leading to redirected lysis of B cell targets without apparent need of costimulation and inducing T cells to proliferate, secrete cytokines and upregulate surface activation markers. TCR-like signalling by MT103 is strictly dependent on the presence of target cells. Redirected lysis of CD19-positive cells by MT103 is seen at low picomolar concentrations and at low effector-to-target ratios. The in-vivo half-life of MT103 is approximately two hours. In the ongoing dose escalation study MT103-104, patients with relapsed B-NHL have so far received continuous infusion of MT103 at maintenance flow-rates of 0.5, 1.5, 5 and 15 μg/m2/24h for 4 or 8 weeks following a 3+3 dose escalation design. Serum concentrations of MT103 remained constant over the entire treatment period at a level depending on the respective maintenance flow-rate. Depletion of circulating B (lymphoma) cells could be observed more frequently with increasing dose levels (DL) from DL1 to DL3, and in all evaluable patients at DL4. Three of six evaluable patients at DL4 showed clinical responses (2 PR, 1 CR) according to standardized Cheson criteria, but no patient of DL1-3. The time courses of absolute CD4 and CD8 T cell counts in peripheral blood were determined by flow cytometry. CD8 T lymphocytes were further subdivided for analysis into naïve T cells, TCM (central memory T cells), TEM (effector memory T cells) and TEMRA (non-proliferating terminally differentiated CTL), and CD4 T lymphocytes into naïve T cells, TCM and TEM. Activation of CD4 and CD8 T cell subsets was determined by measuring upregulation of CD69, CD25 and HLA-DR. Serum levels of cytokines were determined as additional biomarkers for T cell activation. In 50% of patients at DL1 to DL3, CD4 and CD8 T cell counts increased during the course of treatment - over pre-treatment levels. The TEM subset from both CD4 and CD8 T cells accounted for most of the observed increases, while the naïve T cell subsets showed no increase but also no signs of apoptosis. The non-proliferative TEMRA subset of CD8 T cells also remained unchanged in most patients. This indicated that the selective increase of proliferation-competent TEM subsets was attributed to MT103-induced T cell proliferation. At DL4, all evaluable patients showed signs of T cell expansion after 2 weeks of MT103 infusion, which was most pronounced in those who developed a partial or complete remission. The increase of CD8 T cell counts was more pronounced than that of CD4 T cells. T cell expansion was accompanied by upregulation of T cell activation markers as well as by increases in serum concentrations of cytokines like IFN-γ. T cell expansion and activation reverted in all cases when the infusion of MT103 was stopped. In summary, MT103 induced a reversible secondary T cell response involving T cell activation and proliferation as well as T cell cytotoxicity against circulating B cells and lymphoma tissue. The dose-dependent T cell expansion observed during long-term infusion of MT103, particularly within the cytotoxic TEM subset of CD8 T cells, appears to play a key role for clinical activity.

scholarly journals Enhanced Anti-HIV Functional Activity Associated with Gag-Specific CD8 T-Cell Responses

2010 ◽  
Vol 84 (11) ◽  
pp. 5540-5549 ◽  
Author(s):  
B. Julg ◽  
K. L. Williams ◽  
S. Reddy ◽  
K. Bishop ◽  
Y. Qi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Replication ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Cell Counts ◽  
Inhibit Virus Replication

ABSTRACT Effective HIV-specific T-cell immunity requires the ability to inhibit virus replication in the infected host, but the functional characteristics of cells able to mediate this effect are not well defined. Since Gag-specific CD8 T cells have repeatedly been associated with lower viremia, we examined the influence of Gag specificity on the ability of unstimulated CD8 T cells from chronically infected persons to inhibit virus replication in autologous CD4 T cells. Persons with broad (≥6; n = 13) or narrow (≤1; n = 13) Gag-specific responses, as assessed by gamma interferon enzyme-linked immunospot assay, were selected from 288 highly active antiretroviral therapy (HAART)-naive HIV-1 clade C-infected South Africans, matching groups for total magnitude of HIV-specific CD8 T-cell responses and CD4 T-cell counts. CD8 T cells from high Gag responders suppressed in vitro replication of a heterologous HIV strain in autologous CD4 cells more potently than did those from low Gag responders (P < 0.003) and were associated with lower viral loads in vivo (P < 0.002). As previously shown in subjects with low viremia, CD8 T cells from high Gag responders exhibited a more polyfunctional cytokine profile and a stronger ability to proliferate in response to HIV stimulation than did low Gag responders, which mainly exhibited monofunctional CD8 T-cell responses. Furthermore, increased polyfunctionality was significantly correlated with greater inhibition of viral replication in vitro. These data indicate that enhanced suppression of HIV replication is associated with broader targeting of Gag. We conclude that it is not the overall magnitude but rather the breadth, magnitude, and functional capacity of CD8 T-cell responses to certain conserved proteins, like Gag, which predict effective antiviral HIV-specific CD8 T-cell function.

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

2020 ◽  
Vol 4 (1) ◽  
pp. 191-202 ◽  
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.

Clonally-Restricted T-Lymphocytes in PigA Mutant Mice.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2040-2040
Author(s):  
Valeria Visconte ◽  
Nalini Raghavachari ◽  
Keyvan Keyvanfar ◽  
Delong Liu ◽  
Marie Desierto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Immune Function ◽  
Cd8 T Cells ◽  
Bone Marrow Failure ◽  
Hematopoietic Cells ◽  
Cd8 T Cell ◽  
Cell Fraction ◽  
Cell Counts

Abstract Somatic mutation in the X-linked phosphatydylinositol glycan class A (PIG-A) gene causes glycosyl phosphatidylinositol (GPI) anchor deficiency in hematopoietic stem and progenitor cells, in humans, a requirement for the development of the disease paroxysmal nocturnal hemoglobinuria (PNH). While progress has been made in understanding PNH and especially in treatment of intravascular hemolysis secondary to cell surface deficiency of CD59, why PIG-A mutant stem cells expand in the setting of immune-mediated bone marrow failure remains obscure. We produced a conditional PigA knock-out animal model (PigA−/−) by cross-breeding mice carrying germline insertion of two lox sites flanking exon 6 of PigA gene with mice carrying the transgene Cre-recombinase driven by the human c-fes promoter. The resultant B6 Fes-cre PigAflox (PigA−/−) mice had PigA gene inactivation specifically in hematopoietic cells. We observed that GPI-deficient (GPI−) bone marrow (BM) and spleen cells from PigA−/− mice contained much larger proportions of lymphocytes, especially CD8+ T cells, in comparison to GPI+ cells. The expansion of GPI−CD8+ T cells was not associated with any obvious hematological phenotype, and blood and BM cell counts were relatively normal in PigA−/− mice. In comparison to GPI+ cells analyzed by microarray, GPI− BM cells showed up-regulation in expression of genes important for immune function responses. Pathway analysis revealed that differentially-expressed genes were clustered in several groups related to immunological function, such as lymphocyte markers (CD8b1, CD8a, CD3e, CD3d, CD7, CD2, CD5, CD6, CD28, CD96, CD27), proteins related to T cell activation (Lck, Zap70, Fyn, Zeta, Lat, Traf1, Tcf7, Ctla2a/Ctla2b), TCR components (Tcr-beta-V13, Tcr-beta-V8.2, Tcr-alpha, Tcr-beta- J, Tcr-gamma), chemokines and C-C motifs (Ccl5, CXCR6, Ccr7), and molecules of the killer lectin-like receptor subfamily (Klrc1, Klrc2, Klra7, Klra8). We transplanted into lethally-irradiated recipients BM cells from PigA−/− mice (pre-incubated with aerolysin to lyse GPI+ cells) or BM cells from normal PigA+/+ donors. By microarray, transplanted GPI− cells retained the phenotype of untransplanted GPI− cells, with a much increased CD8+ T cell proportion and up-regulated immune function gene expression in comparison to transplanted normal BM cells. The enlarged GPI−CD8+ T cell pool had a significantly lower proportion of CD11a+ cells than did GPI+CD8+ T cells, suggesting that GPI−CD8+ T cells were generally less active. There was no difference in the proportion of CD44− naive T cells between GPI−CD8+ and GPI+CD8+ T cells; GPI−CD8+ T cells were not NK cells as they lacked surface NK1.1 staining. The percentage of CD4+CD25+FoxP3+ regulatory T cells in GPI− cells was only 10% of that in GPI+ cells in peripheral blood in both untransplanted and transplanted animals, indicating that the expanded T cell population in the GPI− cell fraction contained few cells with immunosuppressive property. We further investigated T cell clonality by usage of T cell receptor beta variable region (Vbeta); approximately 5-6 Vbeta subfamilies were over represented in the GPI− CD8+ T cells. In particular, Vbeta 5.1/5.2 was prominent in GPI−CD8+ T cells, constituting 22-23 ± 5% GPI− T cells from untransplanted and transplanted animals; a significant increase in comparison to 8-9.1 ± 0.5% Vbeta 5.1/5.2 clonal representation in GPI+CD8+ T cells. Our results are consistent with an antigen-driven T cell response in the GPI− lymphocyte population, independent of pancytopenia. Functionally, GPI−CD8 T cells showed no response to lectin stimulation as measured by gamma interferon production, but they were capable of effecting target cell apoptosis when co-incubated with minor-H antigen mismatched BM cells in vitro. Our data agrees with observations in humans, in which an immune process driven by a restricted set of (unknown) antigens appears active in the pathogenesis of PNH (Gargiulo et al., Blood 2007). We conclude that deletion of PigA gene in hematopoietic cells, independent of frank hematopoietic failure, leads to enrichment of lymphocytes, especially CD8 T cells, in the GPI− cell fraction that have an inactive and naive phenotype. These expanded, clonally-restricted, T cells may provide an initial pool of immune effectors, which in the proper immune activated environment, contribute to bone marrow failure in PNH.

Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-γ+ HIV-specific T cells during progression to AIDS

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2505-2511 ◽  
Author(s):  
Stefan Kostense ◽  
Kristin Vandenberghe ◽  
Jeanine Joling ◽  
Debbie Van Baarle ◽  
Nening Nanlohy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Activity ◽  
Cd8 T Cell ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
Cytotoxic T Cell ◽  
Cell Counts ◽  
Ifn Γ

Although CD8+ T cells initially suppress human immunodeficiency virus (HIV) replication, cytotoxic T-cell precursor frequencies eventually decline and fail to prevent disease progression. In a longitudinal study including 16 individuals infected with HIV-1, we studied both the number and function of HIV-specific CD8+ T cells by comparing HLA-peptide tetramer staining and peptide-induced interferon-γ (IFN-γ) production. Numbers of IFN-γ–producing T cells declined during progression to acquired immunodeficiency syndrome (AIDS), whereas the number of tetramer+ T cells in many individuals persisted at high frequencies. Loss of IFN-γ–producing T cells correlated with declining CD4+ T-cell counts, consistent with the need of CD4+ T-cell help in maintaining adequate CD8+T-cell function. These data indicate that the loss of HIV-specific CD8+ T-cell activity is not due to physical depletion, but is mainly due to progressively impaired function of HIV-specific CD8+ T cells.

Abstract 585: E3 ubiquitin-protein Ligase Casitas B Lineage Lymphoma b Deficiency Aggravates Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Esther Smeets ◽  
Tom Seijkens ◽  
Myrthe den Toom ◽  
Svenja Meiler ◽  
Esther Lutgens
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Negative Regulator ◽  
Lymphoid Tissues ◽  
Cell Counts ◽  
Macrophage Apoptosis ◽  
Aortic Arches ◽  
B Lineage

E3 ubiquitin ligase Casitas B lineage Lymphoma b (Cbl-b) is a negative regulator in peripheral T cell activation. Cbl-b deficient T cells are hyper-reactive due to CD28-independent activation. Here we studied the effect of Cbl-b deficiency on T cell homeostasis in hypercholesterolemia and on atherogenesis in 20 wk old Cbl-b-/-/ApoE-/- mice. Flow cytometric analysis of lymphoid tissues and aortic arches showed decreased CD4+:CD8+ T cell ratios in Cbl-b-/-/ApoE-/- mice. Cbl-b deficiency induced central memory CD8+ T cells expansion, whereas the proportion of naïve T cells decreased. We found that Cbl-b deficient CD8+ T cells are less apoptotic as indicated by decreased AnnexinV positivity and elevated expression of anti-apoptosis markers, such as Bcl-2. Pro-inflammatory, TNFa and IFNy, and cytotoxicity markers, granzyme B, are increased in Cbl-b deficient CD8+ T cells. As expected from the increase of CD8+ T-cells in the aortic arch, Cbl-b-/-/ApoE-/- mice showed significantly more plaque development in the aortic root. The plaques contained higher leukocyte and T cell counts, but contained surprisingly less macrophages. The latter is caused by decreased monocyte recruitment resulting from lower MCP-1 levels. Moreover, the excess of CD8+ T cells induced enhanced cell death of macrophages. In vitro co-culture of Cbl-b deficient and wildtype CD8+ T cells with bone marrow derived macrophages revealed enhanced macrophage apoptosis in increased CD8+:macrophage ratios, irrespective of the CD8+ T cell genotype. Expression of the M1 macrophage markers, CD115 and CD64 was upregulated in Cbl-b deficient aortic arches, whereas M2 markers, CD206 and Arg-1, were decreased. In conclusion, we show that Cbl-b deficiency decreases CD4+:CD8+ T cell ratio during hypercholesterolemia, through reduced apoptosis and possibly less susceptibility of CD8+ T cells to regulatory T cell suppression. This contributes to exacerbated atherosclerosis in Cbl-b deficient mice. Although plaques contained an excess of lymphocytes and T-cells, and macrophages where of an M1 phenotype, macrophage counts were decreased. This was caused by low MCP-1 levels due to CD8+ T cell induced macrophage apoptosis. These results reveal that Cbl-b balances immune reactions in atherosclerosis.

scholarly journals Immunohematological Reference Ranges for Adults from the Central African Republic

2003 ◽  
Vol 10 (3) ◽  
pp. 443-445 ◽  
Author(s):  
Didier Menard ◽  
Marie Joelle Mandeng ◽  
Mesmin Bem Tothy ◽  
Eric Kassa Kelembho ◽  
Gérard Gresenguet ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Central African Republic ◽  
Cd8 T Cell ◽  
Healthy Adults ◽  
Reference Ranges ◽  
Mean Values ◽  
Cell Counts ◽  
The Absolute ◽  
Hiv Negative

ABSTRACT A survey was carried out on 150 healthy adults to establish hematological reference ranges for human immunodeficiency virus (HIV)-negative adults from the Central African Republic (CAR). Immunohematological mean values, medians, and 95th-percentile reference ranges were established. Mean values were as follows: leukocyte (WBC) counts, 5.28 × 109/liter (males) and 5.11 × 109/liter (females); erythrocyte counts, 5.20 × 1012/liter (males) and 4.50 × 1012/liter (females); hemoglobin, 15.1 g/dl (males) and 12.5 g/dl (females); hematocrit, 45% (males) and 37% (females); lymphocytes, 2,587/μl (males) and 2,466/μl (females); CD4 T cells, 927/μl (males) and 940/μl (females); CD8 T cells, 898/μl (males) and 716/μl (females); and CD4/CD8 T-cell ratio, 1.13 (males) and 1.41 (females). We concluded that (i) the WBC and hemoglobin values of healthy HIV-negative adults from the CAR are lower than the reference values currently used in the CAR and (ii) the absolute CD4 T-cell counts of healthy HIV-negative adults from the CAR are similar to values for Europeans but the absolute CD8 T-cell counts are much higher. Thus, the CD4/CD8 T-cell ratios for healthy adults from the CAR are significantly reduced compared to the ratios for healthy Europeans.

scholarly journals The DARC-null trait is associated with moderate modulation of NK cell profiles and unaltered cytolytic T cell profiles in black South Africans

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242448
Author(s):  
Kewreshini K. Naidoo ◽  
Zesuliwe B. Shangase ◽  
Tabassum Rashid ◽  
Ayanda Ngubane ◽  
Nasreen Ismail ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Full Blood Count ◽  
Cell Counts ◽  
Hiv 1

The Duffy Antigen Receptor for Chemokines (DARC)-null trait, common among persons of African descent and associated with lower absolute neutrophil counts (ANCs), may be linked to increased risk to certain infections including HIV-1 but the underlying causes are poorly understood. We hypothesized that DARC-null-linked neutropenia may negatively impact neutrophil immunoregulatory modulation of other immune cells such as natural killer (NK) and CD8+ T cells leading to altered phenotype, functionality and homeostatic activity of these immune cells. HIV-1 uninfected (n = 20) and HIV-1 chronically infected (n = 19) participants were assessed using multi-parametric flow cytometry to determine NK and CD8+ T cell counts, phenotypic profiles, and cytokine production and degranulation. Annexin V and carboxyfluorescein succinimidyl ester (CFSE) staining were used to examine NK cell survival and NK cell and CD8+ T cell proliferation respectively. Participants were genotyped for the DARC-null polymorphism using allelic discrimination assays and ANCs were measured by full blood count. In HIV uninfected individuals, a reduction of total NK cell counts was noted in the absence of DARC and this correlated with lower ANCs. HIV uninfected DARC-null subjects displayed a less mature NK cell phenotype. However, this did not translate to differences in NK cell activation or effector functionality by DARC state. Whilst HIV-1 infected subjects displayed NK cell profiling that is typical of HIV infection, no differences were noted upon DARC stratification. Similarly, CD8+ T cells from HIV infected individuals displayed phenotypic and functional modulation that is characteristic of HIV infection, but profiling was unaffected by the DARC-null variant irrespective of HIV status. Overall, the data suggests that the DARC-null polymorphism and lower ANCs does not impede downstream cytolytic cell priming and functionality.

scholarly journals Immunohematological Reference Ranges for Adult Ethiopians

1999 ◽  
Vol 6 (3) ◽  
pp. 410-414 ◽  
Author(s):  
Aster Tsegaye ◽  
Tsehaynesh Messele ◽  
Tesfaye Tilahun ◽  
Ermias Hailu ◽  
Tefera Sahlu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cell ◽  
Reference Ranges ◽  
Cross Sectional Survey ◽  
Mean Values ◽  
Cell Ratio ◽  
Cell Counts ◽  
The Absolute ◽  
Hiv Negative

ABSTRACT A cross-sectional survey was carried out with 485 healthy working adult Ethiopians who are participating in a cohort study on the progression of human immunodeficiency virus type 1 (HIV-1) infection to establish hematological reference ranges for adult HIV-negative Ethiopians. In addition, enumeration of absolute numbers and percentages of leukocyte subsets was performed for 142 randomly selected HIV-negative individuals. Immunological results were compared to those of 1,356 healthy HIV-negative Dutch blood donor controls. Immunohematological mean values, medians, and 95th percentile reference ranges were established. Mean values were as follows: leukocyte (WBC) counts, 6.1 × 109/liter (both genders); erythrocyte counts, 5.1 × 1012/liter (males) and 4.5 × 1012/liter (females); hemoglobin, 16.1 (male) and 14.3 (female) g/dl; hematocrit, 48.3% (male) and 42.0% (female); platelets, 205 × 109/liter (both genders); monocytes, 343/μl; granulocytes, 3,057/μl; lymphocytes, 1,857/μl; CD4 T cells, 775/μl; CD8 T cells, 747/μl; CD4/CD8 T-cell ratio, 1.2; T cells, 1,555/μl; B cells, 191/μl; and NK cells, 250/μl. The major conclusions follow. (i) The WBC and platelet values of healthy HIV-negative Ethiopians are lower than the adopted reference values of Ethiopia. (ii) The absolute CD4 T-cell counts of healthy HIV-negative Ethiopians are considerably lower than those of the Dutch controls, while the opposite is true for the absolute CD8 T-cell counts. This results in a significantly reduced CD4/CD8 T-cell ratio for healthy Ethiopians, compared to the ratio for Dutch controls.

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