Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system.
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ABSTRACT:
SUBMITTER: Sinclair C
PROVIDER: S-EPMC3732981 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Model trajectories of CD4+ and CD8+ cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4+?:?CD8+ ratio. DESIGN:Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data. METHODS:We jointly estimated CD4+ and CD8+ cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4+?:?CD8+ ratio trend from this model. We assessed whether CD4+ and CD8+ cell count trends and the CD4+?:?CD8+ ratio trend varied according to CD4+ cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. RESULTS:A total of 39?979 patients were included (median follow-up was 53 months). Among patients with baseline CD4+ cell count at least 50 cells/?l, predicted mean CD8+ cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4+?:?CD8+ ratio. During 15 years of follow-up, normalization of the predicted mean CD4+?:?CD8+ ratio (to >1) was only observed among patients with baseline CD4+ cell count at least 200 cells/?l. A higher baseline CD4+ cell count predicted a shorter time to normalization. CONCLUSION:Declines in CD8+ cell count and increases in CD4+?:?CD8+ ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4+?:?CD8+ ratio is strongly related to baseline CD4+ cell count.
| S-EPMC5991182 | biostudies-literature
Project description:ObjectivesTo analyse the correlation and concordance between aCD4, CD4%, CD4/CD8, their intra-patient variability, and to compare the immune recovery (IR) rates based on the three parameters in HIV-infected patients after starting antiretroviral therapy.MethodsFrom a prospectively followed cohort, patients who maintained HIV-RNA suppression in ?95% of the determinations throughout the follow-up were selected. IR was defined as aCD4 >650/?l, CD4% ?38% or CD4/CD8 ?1.ResultsA total of 1164 patients with a median follow-up of 5 years were analysed. The increases in aCD4, CD4% and CD4/CD8 were highest during the first year and considerably lower thereafter regardless of baseline aCD4. The annual increases in aCD4 showed poor correlations with those of CD4% (r = 0.143-0.250) and CD4/CD8 (r = 0.101-0.192) but were high between CD4% and CD4/CD8 (r = 0.765-0.844; p<0.001). The median intra-annual coefficients of variation for aCD4, CD4/CD8 and CD4% were 12.5, 8.5 and 6.6, respectively. After five years, 66.7%, 41.6% and 42.1% of the patients reached aCD4 >650/?l, CD4% ?38%, and CD4/CD8 ?1, respectively, while only 31% achieved both aCD4 and CD4/CD8 target values.ConclusionsThe increases in aCD4 poorly correlate with those of CD4% and CD4/CD8. IR rates based on aCD4 significantly overstate those obtained by CD4% and CD4/CD8. CD4% and CD4/CD8 are more stable markers than aCD4 and should be taken into account to monitor the IR after treatment initiation.
| S-EPMC6197681 | biostudies-literature
Project description:Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8 < 0.45 in the HIV/HBV coinfected group. A significant increase in the CD8 T cell count was shown up to 24 months after the initiation of effective cART in the subgroup of patients with the worst immune status.
| S-EPMC7889897 | biostudies-literature
Project description:The CD4/CD8 T-cell ratio is emerging as a relevant marker of evolution for many pathologies and therapies. We aimed to explore immunological features beyond CD4/CD8 ratio values in older subjects (>65 years old) who were classified as having lower (<1.4), intermediate (1.4-2), or higher (>2) ratio values. The lower group showed a lower thymic output (sj/β-TREC ratio) and frequency of naïve T-cells, concomitant with increased mature T-cells. In these subjects, the CD4 T-cell subset was enriched in CD95+ but depleted of CD98+ cells. The regulatory T-cell (Treg) compartment was enriched in CTLA-4+ cells. The CD8 T-cell pool exhibited increased frequencies of CD95+ cells but decreased frequencies of integrin-β7+ cells. Interestingly, in the intermediate group, the CD4 pool showed greater differences than the CD8 pool, mostly for cellular senescence. Regarding inflammation, only hsCRP was elevated in the lower group; however, negative correlations between the CD4/CD8 ratio and β2-microglobulin and sCD163 were detected. These subjects displayed trends of more comorbidities and less independence in daily activities. Altogether, our data reveal different thymic output and immune profiles for T-cells across CD4/CD8 ratio values that can define immune capabilities, affecting health status in older individuals. Thus, the CD4/CD8 ratio may be used as an integrative marker of biological age.
| S-EPMC8202849 | biostudies-literature
Project description:Pleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.
| S-EPMC8087817 | biostudies-literature
Project description:Plasma HIV viral load is related to declining CD4 lymphocytes. The extent to which CD8 cells, in addition to RNA viral load, predict the depletion of CD4 cells is not well characterized so far. We examine if CD8 cell count is a prognostic factor for CD4 cell counts during an HIV infection.A longitudinal analysis is conducted using data from the Swiss HIV cohort study collected between January 2000 and October 2014. Linear mixed regression models were applied to observations from HIV-1-infected treatment naive patients (NAIVE) and cART-treated patients to predict the short-term evolution of CD4 cell counts. For each subgroup, it was quantified to which extent CD8 cell counts or CD4/CD8 ratios are prognostic factors for disease progression.In both subgroups, 2500 NAIVE and 8902 cART patients, past CD4 cells are positively (P?<?0.0001) and past viral load is negatively (P?<?0.0001) associated with the outcome. Including additionally past CD8 cell counts improves the fit significantly (P?<?0.0001) and increases the marginal explained variation 31.7% to 40.7% for the NAIVE and from 44.1% to 50.7% for the cART group. The past CD4/CD8 ratio (instead of the past CD8 level) is positively associated with the outcome, increasing the explained variation further to 41.8% for NAIVE and 51.9% for cART.
| S-EPMC5079322 | biostudies-literature
Project description:BackgroundHIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.
| S-EPMC5179051 | biostudies-literature
Project description:ObjectiveStudies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence, it remains unclear whether MVC has unique immunologic effects in comparison with other antiretroviral drugs. We sought to determine whether MVC has differential effects compared with tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy.DesignProspective study in AIDS Clinical Trials Group A5303, a double-blind, placebo-controlled trial (N = 262) of MVC vs. TDF, each combined with boosted darunavir and emtricitabine.MethodsA total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells. Soluble markers were assayed in plasma using ELISA kits. Analyses were as treated.ResultsAnalyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC vs. TDF. A greater CD4 T-cell count increase (median +234 vs. +188 cells/μl, P = 0.036), a smaller CD8 T-cell count decrease (-6 vs. -109 cells/μl, P = 0.008), and a smaller CD4 : CD8 ratio increase (0.26 vs. 0.39, P = 0.003) occurred with MVC. Among participants with a baseline CD4 : CD8 ratio less than 1, a smaller proportion of MVC group normalized to a ratio greater than 1 at week 48 (15 and 36%, P < 0.001).ConclusionMVC resulted in less improvement in the CD4 : CD8 ratio driven by greater increase in CD4 cell count but smaller decline in CD8 cell count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF.
| S-EPMC4966543 | biostudies-literature
Project description:ObjectiveTo investigate the association between current CD4+ T-cell count and CD4/CD8+ ratio with severity of frailty among people aging with HIV.MethodsCross-sectional observational study analysing data from all study visits in the ongoing prospective Modena HIV Metabolic Clinic Cohort between 2006 and 2015. Frailty severity was assessed using a frailty index (FI). We visualized the relationships between frailty index score and current CD4 cell count and CD4/CD8 ratio on two different curves adjusted for age, sex, and duration of HIV infection.ResultsFrailty index scores exhibited an inverse relationship with current CD4 count, up to 900 cells/μL. The CD4/CD8 ratio was inversely correlated with frailty index both below and above the cut-off of 900 CD4 cells/μL.ConclusionsFrailty in PLWH is inversely associated with both immune-activation, depicted by CD4/CD8 ratio and immune-deficit depicted by CD4 count. The first association shows a linear shape while the second shows a hook-shape with a turning point at 900 cells. Above this cut off level CD4 do not represent a significant risk factor for frailty.
| S-EPMC6375603 | biostudies-literature
Project description:IntroductionRituximab (RTX) is a B cell-depleting agent approved for the treatment of granulomatosis with polyangiitis (GPA). RTX reduces antibody producing precursor plasma cells and inhibits B and T cells interaction. Infections related to T cell immunodeficiency are not infrequent during RTX treatment. Our study investigated CD4 cell count and CD4/CD8 ratio in GPA patients during the first two years of long-term RTX treatment.MethodsA single centre cohort study of 35 patients who received median total cumulative dose of cyclophosphamide (CYC) of 15 g and were treated with RTX 2 g followed by retreatment with either 2 g once annually or 1 g biannually. Serum levels of total immunoglobulin (Ig) and lymphocytes subsets were recorded at RTX initiation and at 3, 6, 12, 18 and 24 months. Low CD4 count and inverted CD4/CD8 ratio were defined as CD4 < 0.3 × 10(9)/l and ratio < 1.ResultsThe CD4 cell count and CD4/CD8 ratio decreased slightly following the initial RTX treatment and then increased gradually during maintenance treatment. While the proportion of patients with low CD4 cell count decreased from 43% at baseline to 18% at 24 months, the ratio remained inverted in 40%. Oral daily prednisolone dose at baseline, CYC exposure and the maintenance regimen did not influence the CD4 cell count and ratio. Being older (p = 0.012) and having a higher CRP (p = 0.044) and ESR (p = 0.024) at baseline significantly increased the risk of inverted CD4/CD8 ratio at 24 months. Inverted ratio at baseline associated with lower total Ig levels during the study.ConclusionsOverall, the CD4 and CD4/CD8 ratio increased during maintenance RTX therapy in GPA with no discernible impact of other immunosuppressive therapy. However the increase in CD4 was not followed by an increase in the CD4/CD8 ratio, especially in older patients. Inverted CD4/CD8 ratio associated with lower Ig levels, suggesting a more profound B cell depleting effect of RTX with a relative increase in CD8+ lymphocytes.
| S-EPMC5036106 | biostudies-literature