Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation

Bellissimo, Francesco; Pinzone, Marilia Rita; Celesia, Benedetto Maurizio; Cacopardo, Bruno; Nunnari, Giuseppe

doi:10.2174/1570162x14666160414111554

Cited by 12 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the detailed pathological mechanisms responsible for immunological failure are not completely defined, several parameters have been proposed as strongly associated to an inadequate immune restoration. In particular, age [4,6] nadir CD4+ T cell count [7,8], low CD4/CD8 T cell ratio [9–12], duration of HIV-1 infection [4,6], CD4 and CD8 T cell activation [1], inflammation and microbial translocation [1] have been associated with a failure of immune recovery (reviewed in 2). Moreover, a decrease in circulating naïve CD4 and CD8 T cells [1,13] and a reduction in the response to IL-7 homeostatic stimulation [14–17] have been reported in immunological non responder patients.…”

Section: Introductionmentioning

confidence: 99%

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study

et al. 2019

View full text Add to dashboard Cite

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential.

show abstract

Section: Introductionmentioning

confidence: 99%

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The interaction between CD3 + CD4 + T cells and CD3 + CD8 + T cells changed the ratio of CD3 + CD4 + to CD3 + CD8 + . The ratio of CD3 + CD4 + to CD3 + CD8 + is independently associated with Tcell activation [22][23][24]. The CD3 + CD4 + /CD3 + CD8 + ratio (< 1) has been accepted as a marker of immune system suppression, and is associated with disease such as autoimmune disease, tumors, HIV, etc.…”

Section: Discussionmentioning

confidence: 99%

The role of exogenous CD4+CD25+ Treg cells in heart transplantation tolerance

Zhu

Zheng²

2020

Preprint

View full text Add to dashboard Cite

Background: CD4+CD25+regulatory T cells (CD4+CD25+ Treg cells) play major roles in immune regulation. Previous studies showed CD4+CD25+ Treg cells can maintain peripheral immune tolerance and increase survival time of transplanted organs. However, the biological characteristics and the functional roles of these exogenous CD4+CD25+ Treg cells in transplantation tolerance remain unknown. The current study was conducted to observe the effect of CD4+CD25+ Treg cells on heart allograft in rats and to investigate the underlying mechanism of the exogenous CD4+CD25+ Treg cells.Methods: 5 x 107 spleen cells of SD rats were inoculated into the thymus gland of Wistar rats. The level of CD4+CD25+ Treg cells was examined by the flow cytometry method, and the biological activity of CD4+CD25+ Treg cells was detected by the 3H-TdR method. Hearts were transplanted from SD rats (donors) to Wistar rats (recipients) and the animals were assigned into four groups: HT, HT+Ii,HT+Treg, HT+Treg+Ii. At various time points after the transplantation, the transplanted hearts were collected and histologically examined. The rate of lymphocyte apoptosis and T cell subsets in the peripheral blood of Wistar rats were analyzed with flow cytometry.Results: The CD4+CD25+ Treg cells in Wistar rats were sharply increased. The results show that these exogenous CD4+CD25+ Treg cells have a significant inhibitory effect: the mean survival time of the transplanted hearts was 8.1 ± 1.2 days, 35.7 ± 4.7 days，53.7 ± 6.2 days, 75.7 ± 11.3 days in HT, HT+Ii, HT+Treg, and HT+Ii+Treg group, respectively (n = 12-14/group). Among them, HT vs. HT+Treg and HT vs. HT+Treg+Ii were both significantly different (p < 0.001). In addition, we found that exogenous CD4+CD25+ Treg cells improved the pathological changes of the transplanted hearts, increased the rate of lymphocyte apoptosis, upregulated CD3+CD8+T cells, and suppressed CD3+CD4+ T cells.Conclusions: Exogenous CD4+CD25+ Treg cells appear to induce heart transplantation tolerance. The underlying mechanism is associated with the exogenous CD4+CD25+ Treg cells-dependent induction of lymphocyte apoptosis and modulation of the ratio of T cell subsets.

show abstract

“…More recently, researchers19,20 showed a predictive role for CD4+/CD8 ratio in disease progression and immune activation, also in patients with undetectable HIV RNA21. This issue remains controversial as debatable is, at the same time, the selection of patients to address to this evaluation.…”

Section: Discussionmentioning

confidence: 99%

IS IT SAFE AND COST SAVING TO DEFER THE CD4+ CELL COUNT MONITORING IN STABLE PATIENTS ON ART WITH MORE THAN 350 OR 500 CELLS/µL?

Celesia

Marino

Vecchio

et al. 2019

Mediterr J Hematol Infect Dis

Self Cite

View full text Add to dashboard Cite

BackgroundCD4+ lymphocyte cell count represents the main immunological marker used to monitor HIV infection. However, frequent monitoring may be unnecessary, could cause anxiety to the patient as well as burdening healthcare with extra expenses.Objectives and methodsA two-step retrospective (safety and cost-saving) analysis was performed to evaluate the probability of maintaining a safe number of more than 350 CD4+ cells/μl in HIV-positive subjects under treatment during a three-year follow up and secondarily to estimate in real life the cost of the CD4+ determinations in a 3 years period, speculating on possible cost-saving strategies. The safety analyses was conducted with Kaplan-Meyer method considering: 1) all patients independently from their viral load (VL); 2) patients with 500 > CD4+ ≥ 350 cells/μl versus (vs) CD4+ ≥ 500 cells/μl at baseline; 3) patients with VL < 20 copies/ml vs VL > 20 copies/ml. The cost-saving analysis measuring the costs of CD4+ determinations was calculated from April 1, 2013, to March 31, 2016.ResultsIn the safety analysis, 253 subjects were enrolled. The median CD4+ count was 623 (489–805) cells/μl. Subjects maintaining ≥ 350 cells/μl in the first, second, and third year were respectively 238 (94.1%), 229 (90.5%), and 226 (89.3%), independently from VL. Within subjects with ≥ 350 CD4+/μl vs. ≥ 500 CD4+/μl at baseline, those who maintained ≥ 350 cells/μl until the third year were respectively 241 (95.3%) and 158 (98.1%). The probability of maintaining these values in the third year was 89.3% for those who had CD4+ ≥ 350/μl at baseline and 98.1% for those who had CD4+ ≥ 500/μl. This probability was around 90% vs. 99% for subjects with HIV-RNA above or below 20 copies/ml. In the real-life cost saving analysis, we evaluated subjects with a stable value or more than 500 CD4+ (respectively 343, 364 and 383 in the first, second and third period). We observed mean value of about two determinations patient/year (2.41 in 2013/2014; 2.32 in 2014/2015; 2.18 in 2015/2016), with a significant decrease between the first and the last period (p<0.001). The mean cost patient/year was €101.51 in the first year, €97.61 in the second, €92.00 in the third (p<0,001). Assuming to extend these procedures to all our patients with stable CD4+ cells/μl and monitoring CD4+ cell count once in a year, we were able to obtain an overall saving of €19,152/year.ConclusionsA very high percentage of subjects maintained a high and safe number of CD4+ cells (>350 cells/μl) during a three-year follow-up. It could be possible to save up to 66% of the costs by reducing the number of CD4+ count determinations in a year, to have other favorable consequences as well, releasing new resources for patient management.

show abstract

Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation

Cited by 12 publications

References 0 publications

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study

The role of exogenous CD4+CD25+ Treg cells in heart transplantation tolerance

IS IT SAFE AND COST SAVING TO DEFER THE CD4+ CELL COUNT MONITORING IN STABLE PATIENTS ON ART WITH MORE THAN 350 OR 500 CELLS/µL?

Contact Info

Product

Resources

About