The Effects of Aging on the Rectal Mucosal CD4+ and CD8+ T cell Compartments and the Implications for HIV Transmission Pubblico

Abstract

Men who have sex with men (MSM) remain disproportionately affected by the HIV epidemic in the US, and adolescent and young adult MSM represent a particularly high-risk group. As the vast majority of transmission in MSM occurs through receptive anal intercourse (RAI) (1), one potential reason for discrepant rates of HIV infection among adolescent compared to older MSM is a rectal mucosal immune environment that allows for more efficient viral transmission. In this study comparing immunologic characteristics of the rectal mucosal CD4+ and CD8+ T cell compartments between young MSM, adult MSM, and control males who had never engaged in receptive anal intercourse, we found that young MSM had overall higher levels of viral replication using an ex vivo rectal mucosal explant HIV-1 challenge model compared to adult MSM. Evaluation of CD4+ and CD8+ T cell subsets among the study cohorts revealed greater levels of memory CD4+ T cell proliferation and lower frequencies of IFN-g-and TNF-a-producing CD4+ T cells in both the blood and rectal compartments of young MSM compared to older males, which were findings associated with higher HIV-1 viral replication. These findings suggest that young MSM have a distinct rectal mucosal immune environment that may facilitate HIV transmission. 

Table of Contents

TABLE OF CONTENTS

INTRODUCTION                                                                                          1

BACKGROUND                                                                                             3

METHODS                                                                                                      7

RESULTS                                                                                               11

DISCUSSION                                                                                                  16

REFERENCES                                                                                       22

TABLES/FIGURES                                                                                        25

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Immunology
Parola chiave	Rectal mucosa Adaptive immune system Aging HIV transmission
Committee Chair / Thesis Advisor	Colleen Kelley, Emory University
Committee Members	Matthew Magee, Emory University Ann Chahroudi, Emory University

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