Investigation of CD8+ T Cell Subsets in HIV Infection
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Human immunodeficiency virus (HIV) infection is a pandemic that inflicts great morbidity and mortality. Worldwide, 40 million individuals are living with HIV infection, 5 million new infections occur each year, and more than 3 million individuals die annually as a result of AIDS (1). In the US, AIDS ranks among the top three causes of death for African American men and women aged 25–54 and 35–44 years respectively. California, with 136,000 cases (1981-2002), ranks second nationally in cumulative AIDS cases (2). Approximately 8,000 new HIV infections occur in California each year. Undoubtedly, scientific advances in the prevention and treatment of HIV infection would extend significant improvement to the health and quality of life of millions of people. Intense research efforts have yielded the development of potent antiretroviral therapies (ART) that significantly improve the clinical prognoses of HIV-infected individuals. Indeed, the WHO/UNAIDS initiative of treating 3 million people by the year 2005 (the ‘3 by 5’ campaign) has made the distribution of antiretroviral therapy a global priority. Still, the application of ART does not necessarily prevent new infections and its delivery to the majority of infected persons stands as a formidable challenge. Continued research efforts are required to address these shortcomings and to provide alternative approaches to treatment and prevention. Careful inspection of the natural history of HIV infection provides clues for directing continued research. HIV infection results in a progressive disease caused by the gradual decline of CD4+ T lymphocytes, the cells most vulnerable to infection. The substantial loss of CD4+ T cells leads to a dysfunctional clinical state that allows for the development of opportunistic infections and cancers that are characteristic of acquired immune deficiency syndrome (AIDS). The average time from infection to AIDS is about ten years. As commonly observed in other infections, a minority of HIV-infected individuals exhibit atypical rates of disease progression. Some of these individuals progress rapidly to AIDS, whereas others, termed long-term survivors, remain AIDS-free for periods greater than 15-20 years. In many studies, improved clinical prognoses have been observed to be associated with the immunologic activity of CD8+ T lymphocytes. CD8+ cells are capable of controlling HIV replication through the killing of infected cells, as well as through non-cytotoxic antiviral responses. Still, CD8+ T cell responses have not been characterized well enough to allow for their immunotherapeutic manipulation in the context of HIV infection. To gain better insight into the specifics of the CD8+ T cell response, we will investigate 1) the non-cytotoxic antiviral properties of phenotypically distinct CD8+ T cell subsets, 2) the potential ability of some CD8+ cells to inhibit or regulate the CD8+ cell non-cytotoxic antiviral response, and 3) the ability to induce CD8+ cell non-cytotoxic antiviral activity. The research proposed here, by combining the basic science investigation of CD8+ T lymphocytes and its application to the translational comparison of individuals with disparate courses of disease progression, will forward our understanding of this clinically important cell type. 1. 2004 UNAIDS estimates. 2. 2002 CDC estimates reported in the 2004 SF AIDS Foundation Report.