The HIV-1 Tat protein affects human CD4+ T-cell programing and activation, and favors the differentiation of naïve CD4+ T cells

Nicoli, Francesco; Gallerani, Eleonora; Sforza, Fabio; Finessi, Valentina; Chachage, Mkunde; Geldmacher, Christof; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella; Gavioli, Riccardo

doi:10.1097/qad.0000000000001734

Cited by 17 publications

(19 citation statements)

References 52 publications

(67 reference statements)

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“…Earlier studies proposed that CD57 expression marked terminally differentiated Tmem that underwent activation-induced apoptosis in response to TCR stimulation (7,27), and our results confirm the findings that TCR engagement results in the death of these cells. However, we showed here that terminally differentiated CX3CR1 + CD57 + CD28 -CD8 + Tmem were capable of prolonged survival (via Bcl-2) and proliferation (via mTORC1) in response to IL-15.…”

Section: Discussionsupporting

confidence: 91%

“…CD57 expression has been proposed to mark T cells near the end of their replicative capacity (7,27). Indeed, we found that sorted CX3CR1 + CD57 + CD28 -CD8 + Tmem had decreased viability after 7 days of TCR stimulation (Figure 4, A and B).…”

Section: Resultsmentioning

confidence: 79%

“…Given that CD57 expression is associated with shorter telomeres, increased activation-induced cell death, and poor proliferative potential in response to antigen-mediated stimulation (7,27), we wondered how CD57 + CD8 + Tmem accumulate and persist in CMV + PLWH. To address this, we examined CCR7 -CX3CR1 + CD8 + Tmem for intracellular expression of the prosurvival factor Bcl-2 ( Figure 2A) and the master transcriptional regulator c-myc ( Figure 2B), which is important for stimulating cell cycle progression.…”

Section: Resultsmentioning

confidence: 99%

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"Inflammescent" CX3CR1+CD57+ CD8 T cells are generated and expanded by IL-15

Morris¹,

Chen²,

Mudd³

et al. 2020

JCI Insight

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

"Inflammescent" CX3CR1+CD57+ CD8 T cells are generated and expanded by IL-15

Morris¹,

Chen²,

Mudd³

et al. 2020

JCI Insight

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“…Briefly, whole blood was centrifuged at 2500 rpm (Megafuge 1.0R, Heraeus) for 7 min. to collect plasma, whereas the cellular fraction was loaded on Ficoll density gradient (GE Healthcare) to purify PBMCs, as previously described [29,30]. Plasma was stored at −20 • C and purified PBMCs were suspended in 90% foetal bovine serum (FBS) (Lonza) and 10% DMSO (Sigma-Aldrich) and then preserved in liquid nitrogen until use.…”

Section: Samples Purificationmentioning

confidence: 99%

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

et al. 2020

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Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view.

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“…time points after administration of Tat ( Figure 2 A). Previously, we have reported that Tat favors the late differentiation of T cells [ 38 , 40 , 52 ]. In addition, it has been shown that differentiated (e.g., effector memory) T cells are important correlates of protection in HSV-1 infection [ 16 , 17 , 18 , 19 , 53 ].…”

Section: Resultsmentioning

confidence: 99%

The Tat Protein of HIV-1 Prevents the Loss of HSV-Specific Memory Adaptive Responses and Favors the Control of Viral Reactivation

et al. 2020

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The development of therapeutic strategies to control the reactivation of the Herpes Simplex Virus (HSV) is an unaddressed priority. In this study, we evaluated whether Tat, a HIV-1 protein displaying adjuvant functions, could improve previously established HSV-specific memory responses and prevent viral reactivation. To this aim, mice were infected with non-lethal doses of HSV-1 and, 44 days later, injected or not with Tat. Mice were then monitored to check their health status and measure memory HSV-specific cellular and humoral responses. The appearance of symptoms associated with HSV-reactivation was observed at significantly higher frequencies in the control group than in the Tat-treated mice. In addition, the control animals experienced a time-dependent decrease in HSV-specific Immunoglobulin G (IgG), while the Tat-treated mice maintained antibody titers over time. IgG levels were directly correlated with the number of HSV-specific CD8+ T cells, suggesting an effect of Tat on both arms of the adaptive immunity. Consistent with the maintenance of HSV-specific immune memory, Tat-treated mice showed a better control of HSV-1 re-infection. Although further studies are necessary to assess whether similar effects are observed in other models, these results indicate that Tat exerts a therapeutic effect against latent HSV-1 infection and re-infection by favoring the maintenance of adaptive immunity.

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The HIV-1 Tat protein affects human CD4+ T-cell programing and activation, and favors the differentiation of naïve CD4+ T cells

Abstract: Tat affects the programing and functionality of CD4 T lymphocytes favoring the differentiation of naïve CD4 T cells.

Cited by 17 publications

References 52 publications

"Inflammescent" CX3CR1+CD57+ CD8 T cells are generated and expanded by IL-15

"Inflammescent" CX3CR1+CD57+ CD8 T cells are generated and expanded by IL-15

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

The Tat Protein of HIV-1 Prevents the Loss of HSV-Specific Memory Adaptive Responses and Favors the Control of Viral Reactivation

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