CD25+FoxP3+Memory CD4 T Cells Are Frequent Targets of HIV InfectionIn Vivo

Chachage, Mkunde; Pollakis, Georgios; Kuffour, Edmund Osei; Haase, Kerstin; Bauer, Asli; Nadai, Yuka; Podola, Lilli; Clowes, Petra; Schiemann, Matthias; Henkel, Lynette; Hoffmann, Dieter; Joseph, Sarah; Bhuju, Sabin; Maboko, Leonard; Eberhardt, Kirsten Alexandra; Höelscher, Michael; Feldt, Torsten; Saathoff, Elmar; Geldmacher, Christof

doi:10.1128/jvi.00612-16

Cited by 10 publications

(10 citation statements)

References 77 publications

(93 reference statements)

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“…It has been shown that CXCR3 + and CCR5 + Tregs are recruited to sites with ongoing Th1 inflammation [ 28 , 29 ]. Furthermore, increased expression levels of CCR5 and integrin β7 are associated with higher susceptibility to HIV infection and poor immunological response [ 30 – 32 ].…”

Section: Resultsmentioning

confidence: 99%

Helios + Regulatory T cell frequencies are correlated with control of viral replication and recovery of absolute CD4 T cells counts in early HIV-1 infection

et al. 2017

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BackgroundThe acute phase of HIV infection is characterized by massive depletion of CD4 T cells, high viral plasma levels and pronounced systemic immune activation. Regulatory T cells (Tregs) have the potential to control systemic immune activation but also to suppress antigen specific T and B cell response. The co-expression of FoxP3 and Helios transcription factors, has been described for identification of highly suppressive Tregs. The aim of this study was to characterize the phenotype of classic Tregs during early HIV infection, and to assess the correlations between the frequencies and phenotype of Tregs with the plasma viral load, CD4 counts, immune activation and the frequency of antibodies reactive to HIV-1 proteins, measured by an immunochromatographic test.ResultsThe relative frequency of classic Tregs cells in peripheral blood correlated positively with HIV viral load and immune activation of CD8 T cells, and inversely with absolute CD4 counts and development of anti-HIV antibodies in subjects with early HIV infection. However, the expression of Helios in classic Tregs was inversely correlated with viral replication and immune activation, and positively with recovery of CD4 T cell counts and appearance of antibodies reactive to HIV-1 proteins.ConclusionThese results raise the hypothesis that classic Tregs are inefficient at controlling systemic immune activation in subjects with early HIV infection and may be associated with delayed production of antibodies against HIV proteins, delaying the control of viral replication. Conversely, Helios expressing Tregs might contribute to control of viral replication by mechanisms involving the limitation of systemic immune activation.Electronic supplementary materialThe online version of this article (10.1186/s12865-017-0235-7) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Helios + Regulatory T cell frequencies are correlated with control of viral replication and recovery of absolute CD4 T cells counts in early HIV-1 infection

et al. 2017

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“…These elevated peripheral Treg cell frequencies can result from the reported high rate of conversion of conventional CD4 + T cells into Treg cells during HIV‐1 infection. Moreover, such Treg cells in the context of HIV‐1 infection have also been shown to be significantly more proliferative than other memory CD4 + T‐cell subsets . This coupled with the suggested low susceptibility of peripheral Treg cells to R5 viruses could account for the apparent resistance of Treg cells to destruction by the HIV‐1 in comparison with other CD4 + T‐cell subsets.…”

Section: Discussionmentioning

confidence: 97%

Phenotypic characterization of regulatory T cells from antiretroviral‐naive HIV‐1‐infected people

et al. 2017

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Regulatory T (Treg) cells play a key role in dampening excessive immune activation. However, antiretroviral therapy (ART) -naive HIV-1 infection maintains the immune system in a sustained state of activation that could alter both Treg cell surface markers and functions. As Treg cell surface markers are directly linked to their functions the overall objective of this study was to determine how ART-naive HIV infection affects the phenotypic properties of Treg cells. Our data showed that in ART-naive HIV-1 infection, Treg cells are dominated by effector (CD45RA CD27 CCR7 CD62L ) and effector memory (CD45RA CD27 CCR7 CD62L ) cells. In contrast Treg cells from HIV-negative individuals were mainly naive (CD45RA CD27 CCR7 CD62L ) and central memory (CD45RA CD27 CCR7 CD62L ) cells. Whereas effector and effector memory Treg cells showed enhanced expression of CD39 (P < 0·05), CD73 (P < 0·001), HLA-DR and CD38 (P < 0·001); naive and central memory Treg cells showed a significant reduction in the expression of these markers. Overall Treg cell frequencies within total CD4 T cells correlated positively with plasmatic HIV-1 viral load. As increased viral load is associated with augmented CD4 T-cell destruction; this could suggest a resistance of peripheral Treg cells to HIV-1 destruction. Hence the modulation of Treg cell phenotype and frequencies could be considered in designing immunotherapeutic strategies targeting immune system restoration during HIV-1 infection.

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“…Several studies showed that Treg correlate with decreased levels of T cell activation in HIV-infected patients [34–36], but at least one study showed a positive correlation between Treg proportion in blood and CD4 + T cell activation [37]. On the other hand, Treg may be detrimental by weakening the host immune response against HIV [38, 39] and serving as reservoirs for the virus [40]. However, there is also evidence that Treg directly inhibit HIV replication in activated T cells [41] and that protective HIV-specific CD8 + T cells evade Treg cell suppression [42].…”

Section: Discussionmentioning

confidence: 99%

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

et al. 2017

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BackgroundHIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed.Case presentationA 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4+ T cells and higher percentage of activated CD4+ T cells at HAART initiation. The percentage of memory CD4+ T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8+ T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset.ConclusionAlthough both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2159-x) contains supplementary material, which is available to authorized users.

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CD25⁺FoxP3⁺Memory CD4 T Cells Are Frequent Targets of HIV InfectionIn Vivo

Cited by 10 publications

References 77 publications

Helios + Regulatory T cell frequencies are correlated with control of viral replication and recovery of absolute CD4 T cells counts in early HIV-1 infection

Helios + Regulatory T cell frequencies are correlated with control of viral replication and recovery of absolute CD4 T cells counts in early HIV-1 infection

Phenotypic characterization of regulatory T cells from antiretroviral‐naive HIV‐1‐infected people

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

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