Changes in the haematopoietic progenitor cell compartment in the acquired immunodeficiency syndrome

Ganser, Arnold; Ottmann, Oliver G.; Briesen, Hagen von; Völkers, B.; Rübsamen‐Waigmann, Helga; Hoelzer, Dieter

doi:10.1016/0923-2516(90)90020-j

Cited by 38 publications

(12 citation statements)

References 33 publications

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“…A decrease in CFU-GEMM, CFU-MK, BFU-E, and CFU-GM from bone marrow of patients with AIDS was found to be inversely correlated with the number of circulating CD4 cells and the T4:T8 ratio (21). This observation leads to the conclusion that an imbalance of T cell subpopulations appears to be mainly responsible for the progressive impairment of proliferation and differentiation of bone marrow progenitor cells observed in HIVinfected individuals.…”

Section: Fetalliverhematopoietic Culturesmentioning

confidence: 79%

“…There was an increased number ofBFU-E on d 5 and 10 in HIV-associated cultures when compared to normal controls. Furthermore, phenotype analysis of cultured hematopoietic cells showed a significant increase in the number of CDl4-positive cells on d 10, as well as a significant increase in the number of CD45-positive cells on d 21.…”

Section: Fetalliverhematopoietic Culturesmentioning

confidence: 97%

“…This fact supports our hypothesis that changes observed in the in vitro hematopoiesis of abortuses of HIVseropositive women might be a rebound effect caused by inhibitors produced by the maternal T cell subpopulations or a lack of inhibitors due to a significantly diminished number of early T cells observed in liver tissue of those abortuses. Infection of a small subpopulation of hematopoietic progenitor cells or macrophages could not be excluded in our study, but it is unlikely because infected progenitor cells lose their capacity to proliferate (11 ).…”

Section: Fetalliverhematopoietic Culturesmentioning

confidence: 99%

“…A reduced proliferative capacity in vitro of CFU-GM from the bone marrow of 16 out of 18 patients with AIDS and concurrent neutropenia has been described. Significant reduction of CFU-GEMM, BFU-E, and CFU-MK has also been observed (11).…”

mentioning

confidence: 93%

“…Dysregulation of hematopoiesis by alteration in the T cell subpopulations (11), production of inhibiting glycoproteins (12), antibody-mediated cytotoxicity (13), and infection of hematopoietic progenitor cells by HIV-l (14) have all been implicated as pathogenetic mechanisms. Bone marrow specimens taken from patients with AIDS exhibit myelodysplastic changes (15).…”

mentioning

confidence: 99%

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Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

et al. 1992

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Section: Fetalliverhematopoietic Culturesmentioning

confidence: 79%

Section: Fetalliverhematopoietic Culturesmentioning

confidence: 97%

Section: Fetalliverhematopoietic Culturesmentioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 99%

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Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

et al. 1992

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CD34⁺ and CFU‐GM progenitors are significantly decreased in sivsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction

et al. 1993

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Hematologic abnormalities in the peripheral blood and bone marrow are associated with human immunodeficiency and simian immunodeficiency virus (HIV, SIV) infection. The reasons for these abnormalities remain unclear. Bone marrow specimens collected from uninfected animals (Group A, Controls) and from rhesus macaques experimentally infected with SIVsmm9 during the asymptomatic stage (Group B, SIV+ "well") and during the clinically ill stage (Group C, SIV+ "sick"), underwent a variety of in vitro assays of hematopoiesis. Colony forming unit-granulocyte/macrophage (CFU-GM) per plate growth was 46.7 +/- 7.7, 31.9 +/- 8.4 and 6.5 +/- 5.0 (mean +/- sd, P < .02 each mean compared to the others) in the 3 groups respectively. Burst forming unit-erythroid (BFU-E) growth was similarly decreased in bone marrow samples from the SIV+ animals. There was no change in the number of CFU-GM per plate with the removal of plastic adherent or T-cell mononuclear cell fractions. There was no increase in CFU-GM per plate growth with the addition of low dose GM-CSF (1 or 5 ng/mL) though there was a near 67% increase (48 to 80 CFU-GM per plate) with the addition of 100 ng/mL recombinant rhesus IL-3 and 100 ng/mL GM-CSF in SIV+ "sick" animals. Variation in frequency of CD34+ progenitor cells in SIV+ animals was seen, with 3.0% CD34+ cells in SIV- controls, 4.9% CD34+ cells in SIV+ "well" animals and 0.5% CD34+ progenitor cells in SIV+ "sick" monkeys (P < .01, each mean compared to the others). Finally, there was minimal evidence of SIV sequences by polymerase chain reaction in pooled cultured CFU-GM, and no evidence in flowcytometrically sorted CD34+ progenitor cells from selected animals. Thus, the SIV seropositive rhesus monkey appears to have similar hematopoietic aberrations as are found in HIV infected human subjects and may be an excellent model for studying the interaction of lentiviruses on the kinetics of blood formation.

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Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures

Schwartz

Kessler

Szabo

et al. 1995

Journal of Leukocyte Biology

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This report presents results concerning the potential role of negative regulators in hematopoietic suppression observed in human immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human bone marrow cells. Confluent stromal cell layers established from human bone marrow cells were exposed to HIV-1ADA, a monocytotropic strain of HIV-1. A progressive increase in the concentration of HIV-1 p24 antigen in cultures exposed to HIV-1ADA demonstrated that there was a productive infection. Cells from both noninfected and HIV-infected stromal cell layers produced factors that stimulated the proliferation of colony-forming units for granulocytes and macrophages (CFU-GM) from non-infected CD34+ cells. In contrast, when noninfected CD34+ cells were directly cocultured on intact stromal cell layers fewer CFU-GM and burst-forming units for erythroid cells (BFU-E) were detected in HIV-infected LTC than in noninfected LTC. One week after the addition of CD34+ cells, the number of CFU-GM in HIV-infected LTC in six of nine experiments was reduced compared to noninfected control LTC. In those six experiments, the number of CFU-GM was only 53 +/- 5% (SEM) of the number in noninfected LTC. The number of BFU-E in HIV-1-infected LTC was only 46 +/- 5% of the number in noninfected LTC (n = 5). There were fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced number of CFU-GM. Neutralizing antibody to tumor necrosis factor alpha (TNF-alpha) had no effect on the number of BFU-E in HIV-infected LTC. The number of BFU-E, however, was 2.1 +/- 0.2-fold greater (n = 3) in HIV-infected LTC incubated with neutralizing antibody to interferon-alpha. In HIV-infected LTC with decreased numbers of CFU-GM, the number of CFU-GM was approximately 2-fold greater after incubation of HIV-infected LTC with anti-interleukin-4 (IL-4). The effect of anti-TNF-alpha was variable, and anti-transforming growth factor-beta had no effect on the number of CFU-GM in HIV-infected LTC. After 2 weeks, the number of CFU-GM in HIV-infected LTC incubated with anti-IL-4 and anti-TNF-alpha was 2- to 4-fold greater than in untreated HIV-infected LTC. Antibody treatment did not promote an increase in the number of CFU-GM in noninfected LTC or in LTC in which CFU-GM numbers were not reduced after HIV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

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Changes in the haematopoietic progenitor cell compartment in the acquired immunodeficiency syndrome

Cited by 38 publications

References 33 publications

Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

CD34⁺ and CFU‐GM progenitors are significantly decreased in sivsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction

Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures

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Changes in the haematopoietic progenitor cell compartment in the acquired immunodeficiency syndrome

Cited by 38 publications

References 33 publications

Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

CD34+ and CFU‐GM progenitors are significantly decreased in sivsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction

Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures

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CD34⁺ and CFU‐GM progenitors are significantly decreased in sivsmm9 infected rhesus macaques with minimal evidence of direct viral infection by polymerase chain reaction