Thymic Function Failure Is Associated With Human Immunodeficiency Virus Disease Progression

Ferrando‐Martínez, Sara; Pablo-Bernal, Rebeca S. de; Luna-Romero, M. de; Ory, Santiago Jiménez de; Genebat, Miguel; Pacheco, Yolanda M.; Parras, F; Montero, Marta; Blanco, José Ramón; Gutiérrez, Félix; Santos, Jesús; Vidal, Francisco; Koup, Richard A.; Muñoz‐Fernández, María Ángeles; Leal, Manuel; Ruiz‐Mateos, Ezequiel

doi:10.1093/cid/cix095

Cited by 29 publications

(32 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…showed that INRs had a lower naïve CD4 + T‐cell increase and a lower percentage of CD4 + RTE than immunological responders and healthy controls, indicating that reduced thymic output may be a major mechanism of incomplete immune reconstitution . In accordance, it has been reported that thymic function, measured by the sj/β‐TREC ratio or CD4 + RTE%, can predict HIV‐1 disease progression in HIV‐1‐infected adults and adolescents with perinatally acquired HIV‐1 . These studies indicate that reduced thymic output may play an important role in the incomplete immune reconstitution of HIV‐1‐infected individuals.…”

Section: Potential Mechanisms Of Incomplete Immune Reconstitutionsupporting

confidence: 63%

“…50 In accordance, it has been reported that thymic function, measured by the sj/ -TREC ratio or CD4 + RTE%, can predict HIV-1 disease progression in HIV-1-infected adults and adolescents with perinatally acquired HIV-1. 51,52 These studies indicate that reduced thymic output may play an important role in the incomplete immune reconstitution of HIV-1infected individuals. Conversely, Cobos Jiménez et al found in HIV-1infected ART-experienced 45-year-old adults with detectable viremia (<50 copies/ml) for at least 1 year, the percentage of CD31 + CD4 + cells and Sj-TREC content in PBMCs are much higher than those in healthy controls.…”

Section: Thymus and Naïve Cellsmentioning

confidence: 95%

See 1 more Smart Citation

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Yang

Zhang

et al. 2020

Journal of Leukocyte Biology

191

214

View full text Add to dashboard Cite

The morbidity and mortality of HIV type‐1 (HIV‐1)‐related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV‐1 replication and gradual recovery of CD4+ T‐cell counts. However, ∼10–40% of HIV‐1‐infected individuals fail to achieve normalization of CD4+ T‐cell counts despite persistent virological suppression. These patients are referred to as “inadequate immunological responders,” “immunodiscordant responders,” or “immunological non‐responders (INRs)” who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non‐AIDS events and present higher rates of mortality than HIV‐1‐infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV‐1‐infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.

show abstract

Section: Potential Mechanisms Of Incomplete Immune Reconstitutionsupporting

confidence: 63%

Section: Thymus and Naïve Cellsmentioning

confidence: 95%

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Yang

Zhang

et al. 2020

Journal of Leukocyte Biology

191

214

View full text Add to dashboard Cite

show abstract

“…Among the multiple factors correlated with poor CD4 cell recovery, defective thymic output has been recognized as one of the most important factors (Ferrando-Martinez et al, 2017;Li et al, 2011;Zakhour et al, 2016). Two strategies have been considered to translate this observation into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Two types of poor immunological responder showing distinct responses to long-term HAART

Kong

Tian

et al. 2019

International Journal of Infectious Diseases

View full text Add to dashboard Cite

Most previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART. Methods: This study was designed as an ambispective cohort study, including a 4-5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4-5 years and 6-7 years following HAART initiation. Results: PIRs were subdivided into two populations after 4-5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4 + T cells and CD31 + naïve CD4 + T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output. Conclusions: The two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART.

show abstract

“…As the thymus decreases in size with age, its relative contribution to the peripheral T cell pool remains poorly understood. Several studies support a significant role for the thymus in T cell regeneration, even during aging, most evidently during certain T cell-lymphopenic conditions (Douek et al 1998, Ferrando-Martinez et al 2017.…”

Section: The Effect Of Pregnancy On the Thymusmentioning

confidence: 95%

Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis

Hellberg

2019

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a prerequisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement. The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4 + T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4 + T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment. The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4 + T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAK-STAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31

show abstract

Thymic Function Failure Is Associated With Human Immunodeficiency Virus Disease Progression

Cited by 29 publications

References 33 publications

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Two types of poor immunological responder showing distinct responses to long-term HAART

Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis

Contact Info

Product

Resources

About