Student Theses and Dissertations

Date of Award

2001

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Ho Laboratory

Abstract

The thymus is the primary lymphoid organ responsible for T cell production. It is of particular interest in the context of human immunodeficiency virus (HIV)-l infection, in which the progressive loss of CD4+ T cells leads to immunodeficiency and opportunistic infection. CD4+ T cell loss is thought to result from direct and indirect killing of C D 4 cells in the periphery as well as from pathogenic effects of the virus on the thymus. However, it is not fully understood which is the greater factor in viral-induced CD4+ T cell decay. The development of an assay to detect T cell receptor excisional circles (TREC) as a marker for recent T cell receptor (TCR) recombination in the thymus has proved to be an invaluable tool for the study of recent thymic emigrants. Here we describe the development of this technique in the rhesus macaque model and use this method in combination with other techniques to study the role of the thymus in maintenance of the peripheral T cell pool. This study has two major goals: to define the role of the thymus in peripheral T cell homeostasis in the juvenile rhesus macaque (Macaca mulatto) and to assess the significance of thymic output in the context of simian immunodeficiency virus (SIV) infection. To this end, we have studied the impact of surgical thymectomy on the peripheral T cell pool in a cohort of macaques. W e present evidence that thymic output in the juvenile macaque is measurable but quantitatively insignificant in the context of the total T cell pool. While SIV infection does have pathogenic effects on the thymus, these effects play a minimal role in the overall destruction of the peripheral T cell pool.

Comments

A thesis presented to the faculty of The Rockefeller University in the partial fulfillment of the requirements for the degree of Doctor of Philosophy

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