Date of Award

Fall 9-29-2014

Degree Type

Dissertation

Degree Name

PhD Molecular Bioscience

Department

Biology

Advisor

Sulie L. Chang, PhD

Committee Member

Constantine Bitsaktsis, PhD

Committee Member

Tin-Chun Chu, PhD

Committee Member

Marian Glenn, PhD

Committee Member

Cecilia Marzabadi, PhD

Keywords

HIV, Rat, Transgenic, flow cytometry

Abstract

Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in changes with immune response, immunological phenotypes, and ultimately, increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aged individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. Age matched animals were challenged using lipopolysaccharide (LPS) to determine immunological modification of HIV-1Tg animals throughout the aging process. LPS is known to cause imbalances in cytokine and chemokine release, and provides a method to identify alterations of immune response to bacterial infection. In the HIV-1Tg rats, the percentage of T cells decreased with aging, particularly with T cytotoxic cells, whereas T helper cells were increased with age. Neutrophil and monocyte cell numbers increased in HIV-1Tg rats during maturation compared to age-matched control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α in comparison to age-matched controls. Our data indicate that the immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

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