CD127 Expression in Naive and Memory T Cells in HIV Patients Who Have Undergone Long-Term HAART

Xu, Wenfang; Li, Jie; Yong, Wu; Zhou, Jian‐Kang; Zhong, Jianping; Lv, Qiuqiong; Shao, Hui; Rao, Heping

doi:10.1093/labmed/lmw053

Cited by 14 publications

(12 citation statements)

References 29 publications

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“…As previously described, the percentage of CD127 + cells was slightly higher in CD45RA + than CD45RA -CD4 + T cells ( Figure 5F and refs. 42,43). In addition, MFI analysis of CD127 expression ( Figure 5G and Supplemental Figure 3) showed a slight reduction in CD45RAcells, as previously reported (44).…”

Section: Figure 2 Analysis Of Membrane Domains and Il-7r Distributiosupporting

confidence: 84%

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Pothlichet¹,

Rose²,

Bugault³

et al. 2020

Journal of Clinical Investigation

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Section: Figure 2 Analysis Of Membrane Domains and Il-7r Distributiosupporting

confidence: 84%

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Pothlichet¹,

Rose²,

Bugault³

et al. 2020

Journal of Clinical Investigation

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“…IL-7 signaling through the CD127 receptor is essential for the transition of effector to memory CD4+ T cells as well as the subsequent maintenance of memory cells (32). With ART initiation, the number of CD127+ memory CD4+ T cells increases (29,30,33), most likely due to reductions in inflammation (34). These results suggest a model in which the increase in CD127 expression during ART allows latently infected cells to become long-lived as they now become responsive to IL-7 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

The Replication-Competent HIV-1 Latent Reservoir is Primarily Established Near the Time of Therapy Initiation

Abrahams

Joseph

Garrett

et al. 2019

Preprint

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Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. Little is known about the dynamics of reservoir formation and this reservoir forms even when ART is initiated early after infection. The reservoir of individuals who initiate therapy in chronic infection is generally larger and genetically more diverse than that of individuals who initiate in acute infection, suggesting the reservoir is formed continuously throughout untreated infection. To determine when viruses enter the latent reservoir, we compared sequences of replication-competent viruses from resting CD4+ T cells from nine women on therapy to viral sequences circulating in blood collected longitudinally prior to therapy. We found that 78% of viruses from the latent reservoir were most genetically similar to viruses replicating just prior to therapy initiation. This proportion is far greater than expected if the reservoir forms continuously and is always longlived. Thus, therapy alters the host environment in a way that allows the formation of a majority of the long-lived latent HIV-1 reservoir.

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“…Functionally, memory CD4 + T cells exhibit improved IL-2 release, HIV-1-specific CD4 + T cell responses increase in frequency (100, 109) and CD4 + T cell responses to vaccination improve (101). By comparison, immunological non-responders to ART, in whom viremia is controlled but absolute CD4 + T cells counts are not fully restored, have higher serum IL-7 levels and lower CD127 + CD4 + T cells compared with immunological responders (105, 106, 110). Altogether, in most people ART largely restores CD4 + T cell homeostasis, including CD4 + T cell transition from effector to long-lived memory T cells.…”

Section: Art Restores the Cd4+ T Cell Memory Transitionmentioning

confidence: 95%

“…Elevated turnover of CD4 + T cells is decreased to levels that are comparable with healthy controls (81, 104) within 12 weeks of ART (39, 77). Both absolute CD4 + T cell counts and CD127 + CD4 + memory T cell frequencies increase to levels observed in uninfected individuals (105), though CD127 expression levels on CD4 + T cells remain lower (106). With restoration of absolute CD4 + T cell levels, IL-7 in the serum decreases and IL-7 mediated STAT-5 phosphorylation, which is elevated in memory CD4 + T cells in untreated infection (107), is normalized (108).…”

Section: Art Restores the Cd4+ T Cell Memory Transitionmentioning

confidence: 96%

Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure

et al. 2019

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Recent studies demonstrate that the stable HIV-1 reservoir in resting CD4 + T cells is mostly formed from viruses circulating when combination antiretroviral therapy (ART) is initiated. Here we explore the immunological basis for these observations. Untreated HIV-1 infection is characterized by a progressive depletion of memory CD4 + T cells which mostly express CD127, the α chain of the IL-7 receptor (IL-7R). Depletion results from both direct infection and bystander loss of memory CD4 + T cells in part attributed to dysregulated IL-7/IL-7R signaling. While IL-7/IL7R signaling is not essential for the generation of effector CD4 + T cells from naïve cells, it is essential for the further transition of effectors to memory CD4 + T cells and their subsequent homeostatic maintenance. HIV-1 infection therefore limits the transition of CD4 + T cells from an effector to long-lived memory state. With the onset of ART, virus load (VL) levels rapidly decrease and the frequency of CD127 + CD4 + memory T cells increases, indicating restoration of effector to memory transition in CD4 + T cells. Collectively these data suggest that following ART initiation, HIV-1 infected effector CD4 + T cells transition to long-lived, CD127 + CD4 + T cells forming the majority of the stable HIV-1 reservoir. We propose that combining ART initiation with inhibition of IL-7/IL-7R signaling to block CD4 + T cell memory formation will limit the generation of long-lived HIV-infected CD4 + T cells and reduce the overall size of the stable HIV-1 reservoir.

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CD127 Expression in Naive and Memory T Cells in HIV Patients Who Have Undergone Long-Term HAART

Abstract: CD127 expression in T cells is decreased in patients with HIV-1 and is related to recovery of CD4T-cell counts and to naïve subsets.

Cited by 14 publications

References 29 publications

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

The Replication-Competent HIV-1 Latent Reservoir is Primarily Established Near the Time of Therapy Initiation

Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure

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