CD73+ CD127high long-term memory CD4 T cells are highly proliferative in response to recall antigens and are early targets in HIV-1 infection
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PROVIDER: PRJNA674574 | ENA |
REPOSITORIES: ENA
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Project description:HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4 T cells which highly express the alpha-chain of the receptor for IL-7 (CD127), but not CD38 or Ki-67 in vivo, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease early in HIV-1 infection. We compared gene expression profiles of healthy subjects recovered CD4+CD73+ to CD4+CD73- T cells, and also CD8+CD73+ to CD8+CD73- T cells
2021-02-02 | GSE160805 | GEO
Project description:HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4+ T cells in peripheral blood, which highly express the α-chain of the IL-7 receptor (CD127), but not CD38 or Ki-67, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease very early in HIV-1 infection. Indeed, CD73+ memory CD4+ T cells comprised a median of 7.5% (interquartile range: 4.5-10.4%) of CD4+ T cells in peripheral blood from healthy adults, but were decreased in primary HIV-1 infection to a median of 3.7% (IQR: 2.6-6.4%; p = 0.002); and in chronic HIV-1 infection to 1.9% (IQR: 1.1-3%; p < 0.0001), and were not restored by antiretroviral therapy. Moreover, we found that a significant proportion of CD73+ memory CD4+ T cells were skewed to a gut-homing phenotype, expressing integrins α4 and β7, CXCR3, CCR6, CD161 and CD26. Accordingly, 20% of CD4+ T cells present in gut biopsies were CD73+. In HIV+ subjects, purified CD73+ resting memory CD4+ T cells in PBMC were infected with HIV-1 DNA, determined by real-time PCR, to the same level as for purified CD73-negative CD4+ T cells, both in untreated and treated subjects. Therefore, the proliferative CD73+ subset of memory CD4+ T cells is disproportionately reduced in HIV-1 infection, but, unexpectedly, their IL-7 dependent long-term resting phenotype suggests that residual infected cells in this subset may contribute significantly to the very long-lived HIV proviral DNA reservoir in treated subjects.
| S-EPMC7831934 | biostudies-literature
Project description:Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for HIV infection. Here, we implement a systems approach to discover molecular signatures of HIV latently-infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV cure strategies targeting the hypoxia-CD73-adenosine axis.
2023-09-24 | GSE243577 | GEO
Project description:Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for HIV infection. Here, we implement a systems approach to discover molecular signatures of HIV latently-infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV cure strategies targeting the hypoxia-CD73-adenosine axis.
2023-09-28 | GSE244190 | GEO
Project description:The understanding of heterogeneity of human memory T cells will help to know the function, development and maintenance of memory population, then to improve the recall response or effective immunotherapy. Ecto-5’-nucleotidase CD73 expression in four subsets of memory T cells decreases with aging. The resistance to apoptosis and high expression of IL7R entitle CD73+ memory T cells to be long-lived population. We found antigen-specific memory T cells have overwhelming CD73 expression. The transcriptional and chromatin accessibility profiles indicate the elevated effector functions in CD73+ memory CD4 T cells comparing to CD73- counterparts. Homer analysis and Transcriptional factor (TF)-regulatory element-target gene triplet network clearly show the crucial role of RUNT and NR family TFs in CD73+ cells. Furthermore, CD73+ memory CD4 T cells were prone to differentiate into TRM-like cells under in-vitro sequential TCR and TGF/IL-15 signaling. The decreased percentage of CD73+ memory T cells with age leads to the less replenishment of TRM cells from peripheral blood.
2021-08-28 | GSE157162 | GEO
Project description:The understanding of heterogeneity of human memory T cells will help to know the function, development and maintenance of memory population, then to improve the recall response or effective immunotherapy. Ecto-5’-nucleotidase CD73 expression in four subsets of memory T cells decreases with aging. The resistance to apoptosis and high expression of IL7R entitle CD73+ memory T cells to be long-lived population. We found antigen-specific memory T cells have overwhelming CD73 expression. The transcriptional and chromatin accessibility profiles indicate the elevated effector functions in CD73+ memory CD4 T cells comparing to CD73- counterparts. Homer analysis and Transcriptional factor (TF)-regulatory element-target gene triplet network clearly show the crucial role of RUNT and NR family TFs in CD73+ cells. Furthermore, CD73+ memory CD4 T cells were prone to differentiate into TRM-like cells under in-vitro sequential TCR and TGF/IL-15 signaling. The decreased percentage of CD73+ memory T cells with age leads to the less replenishment of TRM cells from peripheral blood.
2021-08-28 | GSE157163 | GEO
Project description:MSCs are a heterogeneous population and the specific population of MSCs may exhibit a selective ability for tissue repair. The aim of our research was to adapt the CD73+ subgroup of adipose derived MSCs (AD-MSCs) for the therapy of myocardial infarction (MI). Our results revealed that CD73+ AD-MSCs played more effective role in the acceleration function of cardiac recovery by promoting angiogenesis in a rat model of MI compared to mixed AD-MSCs and CD73- AD-MSCs. Microarray analysis shows differences between CD73+ and CD73- AD-MSCs when transcription profile of these two subgroups were compared, especially in VEGF pathway.
2021-06-02 | GSE167219 | GEO
Project description:The objective of this study was to compare recall responses to vaccine antigens at 3 months and 9 months of age in infants who were vaccinated at birth or at 1 month.
2011-06-27 | GSE25263 | GEO
Project description:The objective of this study was to compare recall responses to vaccine antigens at 3 months and 9 months of age in infants who were vaccinated at birth or at 1 month. PBMC were obtained at 9 months of age from infants who were vaccinated at birth (n=25) or 1 month (n=25). The PBMC were cultured in the presence or absence of CRM197 antigen for 72 hours. At the termination of the cultures, total RNA was extracted from the PBMC. The RNA was pooled into groups of n=5 subjects per group, following by labeling and hybridization to Affymetrix microarrays.
2011-06-27 | E-GEOD-25263 | biostudies-arrayexpress
Project description:Vaccination with self and foreign peptides induces weak and strong expansion of antigen-specific CD4 T cells, respectively, but the mechanism is not known. We tested how much the naïve CD4 T cell repertoires specific for self antigens are shaped by negative selection in the thymus by computational analysis of the entire mouse MHCII peptidome and found that negative selection only partially explains the difference between responses to self and foreign. In naïve (uninfected, unimmunized) mice, RNA-Seq identified higher PD1 and CD73 expression on self-specific compared to foreign-specific CD4 T cells. Pharmacological or genetic blockade of PD1 and CD73 significantly increased the vaccine-induced expansion of self-specific CD4 T cells and moved their transcriptomes toward those of foreign-specific CD4 T cells. We conclude that PD1 and CD73 synergistically limit CD4 T cell responses to self. This discovery has implications for the development of tolerogenic vaccines and cancer immunotherapy.
2024-09-16 | GSE263393 | GEO