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Differential effects of Interleukin-7 on normal and HIV-modified T-cell development
AuthorClark, Dawn Rachelle, 1968-
MetadataShow full item record
PublisherThe University of Arizona.
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.
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.
Degree ProgramGraduate College
Microbiology and Immunology