Factors Contributing to HIV-1 Induced Pathogenesis in the Human Thymus

Blom, Bianca; Epeldegui, Marta; Uíttenbogaart, Christel H.

doi:10.5772/21588

Cited by 2 publications

(2 citation statements)

References 220 publications

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“…However, some patients do not experience sufficient T-cell immune restoration despite being aviremic during treatment (2). Regarding T-cell generation in the thymus, HIV-infected patients may display decreased thymopoiesis (3), and thymic dysfunction during HIV infection may be associated with rapid progression in infants with prenatal HIV infection (4). A previous report tested coculture of CD34 + and fetal thymic epithelial cells in the presence or absence of HIV-1, observing that infection led to the inhibition of thymocyte maturation at early stages (CD44 + CD25 − CD3 − ) (5).…”

Section: Introductionmentioning

confidence: 99%

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

Tsukamoto

2019

Front. Immunol.

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HIV-1 causes the loss of CD4+ T cells via depletion or impairment of their production. The latter involves infection of thymocytes, but the involvement of hematopoietic CD34+ cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. In order to have a closer look at the impact of HIV-1 on T-lineage differentiation, this study utilized the OP9-DL1 coculture system, which supports in vitro T-lineage differentiation of human hematopoietic stem/progenitor cells. In the newly developed in vitro OP9-DL1/HIV-1 model, cord-derived CD34+ cells were infected with CXCR4-tropic HIV-1NL4−3 and cocultured. The HIV-infected cocultures exhibited reduced CD4+ T-cell growth at weeks 3–5 post infection compared to autologous uninfected cocultures. Further assays and analyses revealed that CD34+CD7+CXCR4+ cells can be quickly depleted as early as 1 week after infection of the subset, and this was accompanied by the emergence of rare CD34+CD7+CD4+ cells. A subsequent theoretical model analysis suggested potential influence of HIV-1 on the differentiation rate or death rate of lymphoid progenitor cells. These results indicate that CXCR4-tropic HIV-1 strains may impact the dynamics of CD34+CD7+ lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.

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Section: Introductionmentioning

confidence: 99%

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

Tsukamoto

2019

Front. Immunol.

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“…However, some patients fail to show sufficient T-cell immune restoration despite being aviremic during treatment (Corbeau and Reynes, 2011). HIVinfected patients may show decreased thymopoiesis for generation of new T cells (Blom et al, 2011). Thymic dysfunction occurs during HIV disease and is associated with rapid progression in infants with prenatal HIV infection (Ye et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

HIV disrupts CD34⁺progenitors involved in T-cell differentiation

Tsukamoto

2017

Preprint

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HIV-1 causes the loss of CD4+ T cells via depletion or impairment of their production. The latter involves infection of thymocytes, but the involvement of other cells including haematopoietic CD34+ cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. This study utilised the OP9-DL1 coculture system, which supports in vitro T-lineage differentiation of human haematopoietic stem/progenitor cells. Cord-derived CD34+ cells were infected with CXCR4-tropic HIV-1NL4-3 and cocultured. HIV-infected cocultures exhibited sustained viral replication for 5 weeks, as well as reduced CD4+ T-cell growth at weeks 3–5. It was further revealed that CD34+CD7+CXCR4+ cells can be quickly depleted as early as in 1 week after infection of the subset, and this was accompanied by the emergence of CD34+CD7+CD4+ cells. These results indicate that CXCR4-tropic HIV-1 strains may disrupt CD34+CD7+ lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.

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Factors Contributing to HIV-1 Induced Pathogenesis in the Human Thymus

Cited by 2 publications

References 220 publications

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

HIV disrupts CD34⁺progenitors involved in T-cell differentiation

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Factors Contributing to HIV-1 Induced Pathogenesis in the Human Thymus

Cited by 2 publications

References 220 publications

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells

HIV disrupts CD34+progenitors involved in T-cell differentiation

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HIV disrupts CD34⁺progenitors involved in T-cell differentiation