Differential effects of Interleukin-7 on normal and HIV-modified T-cell development

Persistent Link:
http://hdl.handle.net/10150/282118
Title:
Differential effects of Interleukin-7 on normal and HIV-modified T-cell development
Author:
Clark, Dawn Rachelle, 1968-
Issue Date:
1996
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
In this study, an organ culture chimera system was used to study the physiological role of Interleukin-7 (IL-7) in normal T cell development by antibody neutralization of cytokine activity. Additionally, the effect of IL-7 on HIV-modified T cell development was studied. When chimeras were treated with anti-IL-7 for 3 day intervals, a differential effect was observed. Early in culture, when the majority of the cells are CD4/CD8/CD3 triple negative (TN), anti-IL-7 decreased the number of immature and mature cells. The CD44⁺CD25⁺ TN cells were not able to make the transition to the CD44⁻CD25⁺ TN stage without IL-7. In contrast, when IL-7 is neutralized later in the culture period, when the majority of cells are in the double positive (DP) or mature single positive (SP) stages, the number of CD3⁺ cells increases. These data suggest that in addition to its capacity to maintain the viability of the immature cells, IL-7 may actually hold the cells in the immature state. It has been suggested that HIV infection affects the ability to regenerate new T cells. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients and uninfected controls were used as donor cells. The number of mature CD4, CD8 and CD4/8 double positive (DP) cells generated in the cultures derived from HIV-infected PBMC was diminished. This lack of development occurred even with blood from donors with a CD4 count of 1,000/μL. Limit dilution experiments showed that the number of functional precursors in HIV-infected patients is lower than in uninfected patients. The CD3⁻ CD8⁺ and DP T cells were not reduced unless the CD4 count was <250/ml. These data suggest that there is a block in T cell development at the DP stage in cultures derived from PBMC with CD4 counts. IL-7 treatment resulted in a greater loss in the number of T cells produced by infected PBMC. These data show that while IL-7 plays a critical role in normal T cell development, it has the potential to increase the T cell depletion of HIV-infected individuals.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Cell.; Health Sciences, Immunology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Microbiology and Immunology
Degree Grantor:
University of Arizona
Advisor:
DeLuca, Dominick

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleDifferential effects of Interleukin-7 on normal and HIV-modified T-cell developmenten_US
dc.creatorClark, Dawn Rachelle, 1968-en_US
dc.contributor.authorClark, Dawn Rachelle, 1968-en_US
dc.date.issued1996en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIn this study, an organ culture chimera system was used to study the physiological role of Interleukin-7 (IL-7) in normal T cell development by antibody neutralization of cytokine activity. Additionally, the effect of IL-7 on HIV-modified T cell development was studied. When chimeras were treated with anti-IL-7 for 3 day intervals, a differential effect was observed. Early in culture, when the majority of the cells are CD4/CD8/CD3 triple negative (TN), anti-IL-7 decreased the number of immature and mature cells. The CD44⁺CD25⁺ TN cells were not able to make the transition to the CD44⁻CD25⁺ TN stage without IL-7. In contrast, when IL-7 is neutralized later in the culture period, when the majority of cells are in the double positive (DP) or mature single positive (SP) stages, the number of CD3⁺ cells increases. These data suggest that in addition to its capacity to maintain the viability of the immature cells, IL-7 may actually hold the cells in the immature state. It has been suggested that HIV infection affects the ability to regenerate new T cells. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients and uninfected controls were used as donor cells. The number of mature CD4, CD8 and CD4/8 double positive (DP) cells generated in the cultures derived from HIV-infected PBMC was diminished. This lack of development occurred even with blood from donors with a CD4 count of 1,000/μL. Limit dilution experiments showed that the number of functional precursors in HIV-infected patients is lower than in uninfected patients. The CD3⁻ CD8⁺ and DP T cells were not reduced unless the CD4 count was <250/ml. These data suggest that there is a block in T cell development at the DP stage in cultures derived from PBMC with CD4 counts. IL-7 treatment resulted in a greater loss in the number of T cells produced by infected PBMC. These data show that while IL-7 plays a critical role in normal T cell development, it has the potential to increase the T cell depletion of HIV-infected individuals.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Cell.en_US
dc.subjectHealth Sciences, Immunology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorDeLuca, Dominicken_US
dc.identifier.proquest9706153en_US
dc.identifier.bibrecord.b34263305en_US
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