Inhibition of Thymopoiesis of CD34<sup>+</sup>Cell Maturation by HIV‐1 in an In Vitro CD34<sup>+</sup>Cell and Thymic Epithelial Organ Culture Model

Knutsen, Alan P.; Roodman, Stanford T.; Freeman, John J.; Mueller, Kathleen R.; Bouhasin, John D.

doi:10.1002/stem.170327

Cited by 14 publications

(8 citation statements)

References 40 publications

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“…HIV-1 may cause thymocyte depletion mediated by an indirect cytopathic effect and infection of CD3 − CD4 + CD8 − progenitor cells (Su et al, 1995). In an in vitro model imitating the thymic environment, thymocyte maturation was inhibited by HIV infection of the CD44 + CD25 − CD3 − cell lineage (Knutsen et al, 1999). Early ART might preserve the lymphopoiesis capability of the host (Bordoni et al, 2015b(Bordoni et al, , 2018Rb-Silva et al, 2019) and reverse reduced thymic function (Withers-Ward et al, 1997;Levine et al, 2001).…”

Section: The Impact Of Hiv On T-lineage Developmentmentioning

confidence: 99%

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

Tsukamoto

2020

Front. Cell. Infect. Microbiol.

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Section: The Impact Of Hiv On T-lineage Developmentmentioning

confidence: 99%

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

Tsukamoto

2020

Front. Cell. Infect. Microbiol.

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“…Evidence for the direct infection of thymocytes with HIV-1 has been provided with the use of fetal thymic organ cultures (FTOC), and in thymocyte/TEC suspension cultures. Thymocytes in these cultures are able to support high levels of HIV replication [13][14][15][16]. The ability of HIV to infect thymocytes in vitro was dependant on direct contact between thymocytes and TEC [4].…”

Section: Introductionmentioning

confidence: 99%

An In vitro Model for the Study of HIV Infection of Thymocytes

Young

Angel²

2013

J Clin Cell Immunol

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The study of human thymocytes requires an appropriate matrix to enable the proper function of thymocytes. Although OP9-DL1 cells have been well established as an ideal co-culture system for the generation of T-cells from their progenitors; their ability to support a mixed population of mature human thymocytes for in vitro HIV infection studies has yet to be established. We assessed the effects of co-culturing a heterogeneous population of mature human thymocytes with a mouse derived cell line (OP9) transduced with the notch ligand delta like 1 (OP9-DL-1) and compared this to standard co-culture with human thymic epithelial cells (TEC). Co-culturing thymocytes with OP9-DL1 cells resulted in higher viability and lower apoptosis when compared to TEC co-cultures. The subset distribution and CD127 expression of thymocytes varied slightly between conditions. Thymocytes co-cultured with OP9-DL1 cells had a lower proportion of CD3 + DP cells and higher proportion of SP4 cells compared to TEC co-cultures. The mature CD3 + CD4 + CD8-(SP4) cells also had lower levels of CD127 expression in OP9-DL1 cultures when compared to TEC. Interleukin-7 stimulation of thymocytes resulted in a decrease in CD127 expression in OP9-DL1 co-cultures, as previously observed with TEC co-cultures. Thymocytes co-cultured with OP9-DL1 tended to have higher levels of IL-7 induced STAT-5 phosphorylation and had higher levels of Interleukin-7 induced Bcl-2 expression. OP9-DL1 cells provide a microenvironment which is permissive to HIV infection in thymocytes in vitro. Co-culturing thymocytes with OP9-DL1 will facilitate the study of human thymocytes and aid in the study of exogenous stimuli or infection on individual thymocyte subsets.

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“…[12][13][14] Decreases in the pool of early progenitor stem cells, including the most primitive CD34 ϩ hematopoietic BM cells, may also limit T-cell regeneration. 15,16 Indeed hematologic abnormalities are frequently observed during HIV infection and BM dysfunction probably contributes to the observed cytopenia. 17 Intercurrent infections, antiviral drugs, 18 and the antibiotics commonly used in patients with AIDS may all affect the production of blood cells.…”

Section: Introductionmentioning

confidence: 99%

Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques

Thiébot

Vaslin

Derdouch

et al. 2005

Blood

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IntroductionHIV type 1 (HIV-1) infection typically involves a progressive loss of blood CD4 ϩ T lymphocytes, associated with functional T-cell abnormalities and immunodeficiency. There may be several reasons for the decrease in CD4 ϩ T-cell counts, including direct and indirect virus-mediated cell destruction and defective homeostasis. 1,2 The half-life of peripheral blood T cells, which is approximately 82 days in healthy individuals, is more than 50 days shorter in HIV-infected patients 3 and T-cell numbers appear to be maintained at high levels principally by an increase in the production of CD8 ϩ T cells.Different mechanisms have been proposed for explaining defective production of T lymphocytes, including deregulated thymus activity, infection, and depletion of immature thymocytes expressing CD4 and alteration of early progenitors including at the level of bone marrow (BM) CD34 ϩ precursors. To our knowledge, this last point has never been clearly addressed and was therefore the purpose of our work.Defective de novo production of T lymphocytes by the thymus may make a significant contribution to CD4 ϩ T-cell lymphopenia. In HIV infection, a low proportion of recent thymic emigrants, with episomal DNA formed by rearrangement of the T-cell receptor genes (TREC), 4 is correlated with disease progression, although the value of quantitative TREC measurement in HIV-seropositive patients remains unclear. 5,6 Highly active antiretroviral therapy (HAART) helps to increase the number of CD4 ϩ T cells in the periphery, probably due to both the expansion and redistribution of cell populations present in lymphoid tissues and the de novo generation of T lymphocytes by the thymus. 7-9 T-cell counts are restored to high levels in a biphasic manner following the initiation of HAART. There is an initial rapid increase in the numbers of CD4 ϩ and CD8 ϩ T cells of the memory phenotype (CD45RO ϩ ), and then the proportion of naive T cells (CD45RA ϩ CD62L ϩ ) increases. 7 Changes in thymus volume and an increase in TREC levels in the periphery 10 also provide evidence that successful HAART increases thymus activity. 11 However, CD4 ϩ T-cell counts remain below normal values in treated patients, suggesting that thymic production is not completely restored and is not necessarily associated with an increase in lymphocyte half-life 3 and the complete restoration of efficient antiviral immunity.Changes in thymus function in patients infected with HIV-1 result directly from degeneration of the stroma, infection of immature thymocytes, and dysregulation of thymocyte/stromal cell interactions. [12][13][14] Decreases in the pool of early progenitor stem cells, including the most primitive CD34 ϩ hematopoietic BM cells, may also limit T-cell regeneration. 15 18 and the antibiotics commonly used in patients with AIDS may all affect the production of blood cells. However, although hematopoietic cells do not seem to undergo direct infection with HIV, they may be directly damaged due to the inhibitory effect of HIV-related proteins 19 or proi...

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Inhibition of Thymopoiesis of CD34⁺Cell Maturation by HIV‐1 in an In Vitro CD34⁺Cell and Thymic Epithelial Organ Culture Model

Cited by 14 publications

References 40 publications

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

An In vitro Model for the Study of HIV Infection of Thymocytes

Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques

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Inhibition of Thymopoiesis of CD34+Cell Maturation by HIV‐1 in an In Vitro CD34+Cell and Thymic Epithelial Organ Culture Model

Cited by 14 publications

References 40 publications

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

Hematopoietic Stem/Progenitor Cells and the Pathogenesis of HIV/AIDS

An In vitro Model for the Study of HIV Infection of Thymocytes

Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques

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Inhibition of Thymopoiesis of CD34⁺Cell Maturation by HIV‐1 in an In Vitro CD34⁺Cell and Thymic Epithelial Organ Culture Model