Peripheral T follicular helper Cells Make a Difference in HIV Reservoir Size between Elite Controllers and Patients on Successful cART

García, Marcial; Górgolas, Miguel; Cabello, Alfonso; Estrada, Vicente; Ligos, José Manuel; Fernández-Guerrero, Manuel L.; Barros, Carlos; López-Bernaldo, Juan Carlos; Hera, Francisco Javier De La; Montoya, Marı́a C.; Benito, José M.; Rallón, Norma

doi:10.1038/s41598-017-17057-y

Cited by 24 publications

(20 citation statements)

References 45 publications

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“…Patients were recruited from four different hospitals in Madrid, Spain, during a period of 12 months. Inclusion criteria for HIV patients have been described elsewhere 47 . A group of 10 uninfected subjects were also included as control group (HC group).…”

Section: Methodsmentioning

confidence: 99%

“…Starting form fresh peripheral blood mononuclear cells (PBMCs), two different subsets of CD4 T-cells were purified: resting memory CD4 T (Trm) cells (defined as CD4+CD45RO+CD25−CD69−HLADR−) and peripheral T follicular helper (pTfh) cells (defined as CD4+ CD45RO+ CXCR5+). For this purpose, immunomagnetic separation was employed as has been described elsewhere 47 . Purity of each CD4 subset was tested by flow cytometry using a Sony Spectral flow cytometer.…”

Section: Methodsmentioning

confidence: 99%

“…Total cellular DNA was extracted using a QiAmp DNA Mini-Kit following manufacturer instructions. Content of HIV DNA (expressed as copies of HIV-DNA per million cells) was quantified using an ultrasensitive digital droplet PCR (ddPCR) as has been already described 47 .…”

Section: Methodsmentioning

confidence: 99%

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CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

García

Navarrete-Muñoz

Ligos

et al. 2018

Sci Rep

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A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = −0.46, p = 0.043) and of CCR6 (rho = −0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

García

Navarrete-Muñoz

Ligos

et al. 2018

Sci Rep

Self Cite

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show abstract

“…The observed decline of cellassociated RNA may reflect the relative instability of effector cells, including PD-1+CD4+ T cells, which express viral proteins, or a decrease in the number of infectious virions that remain on FDCs within GC, thereby limiting new and preferential infection of Tfh [9]. In peripheral blood, Garcia et al reported no differences in HIV DNA concentrations between cells with a Tfh phenotype and those without a Tfh phenotype in either elite controllers or virologically suppressed individuals on ART [21]. Whether peripheral blood cells with a Tfh phenotype truly reflect lymphoid tissue Tfh has not been firmly established, although a clonal relationship was recently reported between these subsets [22**].…”

Section: Role Of Follicular T Cells In Hiv Infection Replication Anmentioning

confidence: 99%

Follicular T-cell subsets in HIV infection

Ollerton

Connick

2019

Current Opinion in HIV and AIDS

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Purpose of review-T cells within B cell follicles of secondary lymphoid tissues play key roles in HIV immunopathogenesis. This review highlights recent findings and identifies gaps in current knowledge. Recent findings-B cell follicles are major sites of virus replication and demonstrate significant impairments in generation of humoral immunity in HIV infection. Follicular T helper cells (Tfh), follicular T regulatory cells (Tfr) and follicular CD8 T cells (fCD8) play key roles in HIV immunopathogenesis. Tfh and more recently Tfr are highly permissive to HIV, and may serve as reservoirs of HIV in treated infection. Virus-specific CD8 T cells are less abundant in B cell follicles than extrafollicular regions, but their effector mechanisms remain an area of significant controversy. Impairments in Tfh likely contribute to impaired humoral immunity and potential mechanisms include B cell counter-regulatory mechanisms, Tfr suppression, and diminished repertoire breadth. A better understanding of the roles of Tfh, Tfr and fCD8 in HIV immunopathogenesis is critical to development of effective HIV vaccines and cure strategies. Summary-Tfh, Tfr, and fCD8 contribute to HIV persistence and impaired humoral immunity. A better understanding of their roles could facilitate vaccine development and HIV cure strategies.

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“…Boritz and colleagues studied the persistence of virus in HIV controllers and found that, despite effective antiviral immune responses in these individuals, their reservoir was maintained through viral replication, clonal expansion of latently infected cells, and a low level of circulating infected cells 57 . However, it was recently demonstrated that the HIV reservoir is smaller in elite controllers, particularly in peripheral T follicular helper cells, meaning the host response within these controllers is able to limit the HIV reservoir size 58 . The HIV reservoir found in lymphoid tissue is a major barrier to current CD8 T-cell-based cure efforts because without effective immune responses or daily ART, these latently infected cells reactivate and virus rebounds.…”

Section: Future Directionsmentioning

confidence: 99%

Understanding the CD8 T-cell response in natural HIV control

Boppana

Goepfert

2018

F1000Res

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HIV-infected individuals who maintain control of virus without antiretroviral therapy (ART) are called HIV controllers. The immune responses of these individuals suppress HIV viral replication to low levels or, in the case of elite controllers, to undetectable levels. Although some research indicates a role for inferior virulence of the infecting viral strain in natural control, perhaps by way of defective Nef protein function, we find that the majority of research in HIV controllers highlights CD8 T cells as the main suppressor of viral replication. The most convincing evidence for this argument lies in the strong correlation between certain HLA-I alleles, especially B*57, and HIV control status, a finding that has been replicated by many groups. However, natural control can also occur in individuals lacking these specific HLA alleles, and our understanding of what constitutes an effective CD8 T-cell response remains an incomplete picture. Recent research has broadened our understanding of natural HIV control by illustrating the interactions between different immune cells, including innate immune effectors and antigen-presenting cells. For many years, the immune responses of the natural HIV controllers have been studied for clues on how to achieve functional cure in the rest of the HIV-infected population. The goal of a future functional cure to HIV is one where HIV-infected individuals’ immune responses are able to suppress virus long-term without requiring ART. This review highlights recent advances in our understanding of how HIV controllers’ natural immune responses are able to suppress virus.

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Peripheral T follicular helper Cells Make a Difference in HIV Reservoir Size between Elite Controllers and Patients on Successful cART

Cited by 24 publications

References 45 publications

CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

Follicular T-cell subsets in HIV infection

Understanding the CD8 T-cell response in natural HIV control

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