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Background Immune system dysfunction has been associated with depressive disorders; however, the specific alterations in CD4 + T lymphocytes and cytokines among individuals with varying severities of depression remain unclear. This study aimed to investigate the immunological changes in patients with mild, moderate, and severe depression, to identify potential biomarkers for clinical diagnosis and disease severity assessment, and to uncover the immunological mechanisms involved in depression. Methods Twenty-eight mild depression patients, thirty-one moderate depression patients, twenty-two severe depression patients and eighty-three healthy subjects were included in the mild, moderate, severe and control group. The relative proportions and absolute quantities of Th1, Th2, Th17 and Treg cells in peripheral blood were determined by flow cytometry. In addition, the levels of cytokines in serum were detected by cytometric bead array (CBA), including IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α. Results The levels of Th1%, Th17, Th1/Th2, and Th17/Treg ratios were significantly higher in the mild depression group compared to the control group ( p  < 0.05), with a concurrent decrease in Treg% ( p  < 0.05). In the moderate depression group, elevated levels of Th1%, Th17%, Th1, Th17, Th1/Th2, and Th17/Treg were observed ( p  < 0.05), alongside reduced Treg% and Treg counts ( p  < 0.05). The severe depression group exhibited further increases in Th1%, Th17%, Th1, Th17, Th1/Th2, and Th17/Treg ( p  < 0.05). IL-4 levels progressively decreased, while IL-6 levels increased across the mild, moderate, and severe depression groups ( p  < 0.05). A negative correlation was found between depression severity and IL-4 ( r = -0.544, p  < 0.001), and a positive correlation with IL-6 ( r  = 0.553, p  < 0.001). IL-4 and IL-6 were identified as independent factors influencing depression severity ( p  < 0.01). Conclusions The study’s findings suggest that abnormalities in CD4 + T lymphocytes and cytokines are characteristic of depression across its severity spectrum, with an increase in Th1 and Th17 cells and a decrease in Treg cells. IL-4 and IL-6 may serve as indicators of depression severity and are significant biomarkers for assessing disease progression. These insights enhance our understanding of the immunological basis of depression and provide novel strategies for its management and treatment.

Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15–30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target.

Some people with Human Immunodeficiency Virus (HIV) on effective antiretroviral therapy have persistent low lymphocyte CD4 counts and remain at an increased risk of Acquired Immunodeficiency Syndrome (AIDS). We investigated whether primary drug resistance mutations (DRMs) and HIV-1 subtype could be related to immunologic reconstitution in these people. In a multicenter, observational cohort study among treatment-naïve patients, we analyzed HIV-1 subtype, primary drug resistance mutations, CD4 counts, and CD4:CD8 ratios during effective antiretroviral therapy. We compared these variables between patients with different HIV subtypes and between those with or without drug-resistance mutations up to 48 weeks post-baseline. In 156 patients, CD4 count normalization (≥500 cells/µL) was observed in 39% of patients, while CD4:CD8 ratio ≥ 1 in 27% after treatment implementation. HIV-1 subtype B was present in 75% of the patients and subtype A in 22%. Primary resistance mutations were found in 57% of the individuals. The percentage of immunological nonrespondents did not differ significantly between those with different HIV subtypes or between those with or without primary resistance mutations (p > 0.05). In conclusion, there was no significant coincidence between the HIV subtype and primary drug resistance mutations with immunological reconstitution in patients receiving effective antiretroviral therapy.

The Mokola Virus belongs to the family Rhabdoviridae and is genotype 3 of the Lyssavirus genera. A small number of cases of animal and human encephalomyelitis, mainly scattered over sub-Saharan Africa, have been linked to the Mokola Virus (MOKV). Currently there is no vaccine to protect against MOKV infection in people or animals. It has been proven that rabies vaccination does not confer immunity against MOKV infection, even though MOKV and the rabies virus are related. Using immunoinformatics approaches, this study designed an mRNA vaccine that can protect against all the five glycoproteins of the Mokola virus. NCBI was used to obtain the viral sequences, which were then screened for antigenicity, allergenicity, toxicity, B-cell epitopes, CD8 + T lymphocytes (CTL), and CD4 + T lymphocytes (HTL). These epitopes were used in the construction of the vaccine. Some extra co-translational residues were added to the mRNA vaccine construct. Its molecular weight is 129.19083 kDa, and its estimated pI is 8.58. It interacts rather steadily and with limited deformability with TLR 3, among other human innate immune receptors. Overall, the results show that the produced candidate vaccine is non-allergen, non-toxic, and can elicit T–cell and B–cell immune responses. These findings can further be subjected to in-vivo and in-vitro techniques for validation.

Background Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are the most common types of leukemia in adults with an overall poor prognosis. PD-1 alone or combined with other immune checkpoint blockade is a promising research direction for the treatment of acute leukemia (AL) patients. However, clinical Implications of aberrant PD-1 expression in peripheral CD4+ and CD8+ T lymphocytes of AML and ALL patients in assessing the prognosis of diseases, remains inconclusive. Methods In the present study, we used flow cytometry to evaluate PD-1 expression on the surface of CD4+ and CD8+ T lymphocytes in the peripheral circulation of AML and ALL patients and its clinical significance. A total of 53 AML patients, 44 ALL patients and 28 healthy controls were enrolled in this study and peripheral blood specimens were detected by flow cytometry. Results Our results indicated that percentages of CD4+ PD1+ and CD8+ PD1+ T lymphocytes in newly diagnosed and non-remission groups were significantly higher than healthy control both in AML and ALL patients. The high level of CD4+ PD1+ and CD8+ PD1+ T lymphocytes were respectively poor prognostic indicators of AML patients and ALL patients but had no significant correlation with most common clinical risks. Conclusions Our findings show that aberrant PD-1 expression correlates with the prognosis of AL patient and may thus serve as poor prognostic indicators. Immunotherapy using PD-1 inhibitors may be a promising strategy for AML and ALL patients with peripheral circulating CD4+ PD1+ and CD8+ PD1+ T lymphocytes positively expressed, respectively.

Background HLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder for which many autoantigens have been described. Results Using multi-parameter flow cytometry, we developed a multi-HLA class II tetramer approach to simultaneously study several antigen specificities in RA patient samples. We focused on previously described citrullinated HLA-DRB1*04:01-restricted T cell epitopes from α-enolase, fibrinogen-β, vimentin as well as cartilage intermediate layer protein (CILP). First, we examined inter-assay variability and the sensitivity of the assay in peripheral blood from healthy donors ( n  = 7). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws ( n  = 14). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia ( n  = 5) and early RA patients ( n  = 5) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients ( n  = 10) and found that the group of patients achieving minimum disease activity (DAS28 < 2.6) at 6 months follow-up displayed a decrease in the frequency of citrulline-specific T cells. Conclusions Our study demonstrates the development of a sensitive tetramer panel allowing simultaneous characterisation of antigen-specific T cells in ex vivo patient samples including RA ‘at risk’ subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens.

Background Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. Methods The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection. Results We found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. Conclusions Pre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.

CD32a has been proposed as a specific marker of latently HIV-infected CD4 T cells. However, CD32a was recently found to be expressed on CD4 T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a CD4 T cells during HIV infection. To this end, we analyzed CD32a CD4 T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors. We found that CD32a CD4 T cells include heterogeneous subsets that are differentially affected by HIV infection. Our analysis revealed that naive ( ), central memory ( ), and effector/memory ( ) CD32a CD4 T-cell clusters that co-express LILRA2- and CD64-activating receptors were more abundant in primary HIV infection and cART stages. Conversely, LILRA2 CD32a CD4 T-cell clusters of either the T , T , or T phenotype were more abundant in healthy individuals. Finally, an activated CD32a CD4 T cell cluster co-expressing LILRA2, CD57, and NKG2C was more abundant in all HIV stages, particularly during primary HIV infection. Overall, our data show that multiple abundance modifications of CD32a CD4 T-cell subsets occur in the early phase of HIV infection, and some of which are conserved after effective cART. Our study brings a better comprehension of the relationship between CD32a expression and CD4 T cells during HIV infection.

Background An anti‐HIV‐1 tat ribozyme, termed Rz2, has been shown to inhibit HIV‐1 infection/replication and to decrease HIV‐1‐induced pathogenicity in T‐lymphocyte cell lines and normal peripheral blood T‐lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. Methods Apheresis was used to obtain a peripheral blood cell population from each of four HIV‐negative donors. After enrichment for CD4+ T‐lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme‐containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV‐1‐positive twin recipient. Marking was assessed over an initial 24‐week period and in total over an approximate 4‐year period. Results The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2‐ and LNL6‐gene‐containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T‐lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. Conclusions The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T‐lymphocytes containing an anti‐HIV gene construct may impact on HIV‐1 viral load and CD4+ T‐lymphocyte count, potentially representing a new therapeutic modality for HIV‐1 infection. Copyright © 2005 John Wiley & Sons, Ltd.

The global impact of HIV is especially significant when diagnoses are made in advanced stages. While strategies exist to mitigate late presentations, Ecuador’s 2018–2022 strategic plan has not yet been evaluated. This study assesses the prevalence and implications of late and advanced HIV presentations in Ecuador, using data from a reference hospital in Quito. A cross-sectional analysis of 436 medical records of people living with HIV from the “Hospital de Especialidades Eugenio Espejo” was conducted between November 2015 and February 2020. The data were divided into “Pre-Plan” and “Post-Plan” periods for comparative analysis. The mean CD4 T count showed a non-statistically significant increase in the post-plan period (January 2018–February 2020). Notably, 65.1% of patients presented late, and 39.4% had advanced disease. Demographic data indicated that 89.9% were men, and 54.1% were under 30 years of age. No characteristics were identified that were associated with advanced late presentation of HIV infection. Sexual orientation data revealed that 69.1% identified as homosexual or bisexual. A predominance of late and advanced presenters was identified in the post-plan period, associated with being employed (p < 0.05) and being drug users (p < 0.001). There was also a greater incidence of late presenters among immigrants in the post-plan period (p = 0.045). Despite the implementation of Ecuador’s 2018–2022 strategic plan for HIV, substantial challenges in reducing late presentations remain. This study suggests that early diagnoses have not significantly improved. Employed patients and drug users were more likely to present late, with drug users also accounting for many advanced cases. This study highlights the need for more focused and targeted strategies to supplement the existing plan.