RRC ID 60105
Author Tsukamoto T.
Title HIV Impacts CD34+ Progenitors Involved in T-Cell Differentiation During Coculture With Mouse Stromal OP9-DL1 Cells.
Journal Front Immunol
Abstract 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.
Volume 10
Pages 81
Published 2019-1-1
DOI 10.3389/fimmu.2019.00081
PMID 30761146
PMC PMC6361802
MeSH Acquired Immunodeficiency Syndrome / metabolism Animals Antigens, CD34 / metabolism* Antigens, CD7 / metabolism CD4-Positive T-Lymphocytes / metabolism* Cell Differentiation* Cell Lineage Coculture Techniques Fetal Blood / cytology HEK293 Cells HIV-1 / genetics HIV-1 / metabolism* Hematopoietic Stem Cells / metabolism* Humans Mice Models, Biological Receptors, CXCR4 / metabolism Stromal Cells / metabolism*
IF 4.716
Times Cited 5
Human and Animal Cells OP9(RCB1124)