Immunological and Virological Effects of PD-1 Blockade Post ART Interruption In the Blood of Chronically SIV Infected Indian Rhesus Macaques Open Access

Abstract

Chronic immunodeficiency virus infections are characterized by dysfunctional cellular antiviral immune responses. Virus-specific CD8 T cells progressively become exhausted and hierarchically lose functions such as abilities to proliferate and produce cytokines. Previous studies in various study models have shown that PD-1 inhibitory pathway could be targeted. In vivo PD-1 blockade in chronically simian immunodeficiency virus (SIV) infected rhesus macaques resulted in enhancement of immunological responses of SIV-specific CD8 T cells. Here we studied the immunological and virological effects of in vivo PD-1 blockade post antiretroviral therapy interruption (ART). Sixteen weeks after SIV infection Eleven Indian rhesus macaques received 21 weeks of ART. The administration of anti-PD-1 antibody was initiated four weeks after ART interruption. Mamu-A*01 tetramer was used to detect CD 8 T cells specific against immunodominant epitope Gag CM9 in the blood. The results show that PD-1 blockade post ART interruption resulted in a rapid decline in plasma viral load in four out of the seven anti-PD-1 antibody treated macaques. PD-1 blockade did not expand the frequency of Gag CM9-specific CD8 T cells, but increased the frequency of central memory-like CD8 T cells with high costimulatory and lymph node homing potential that could terminally differentiate into effector memory population to combat SIV infection. The findings suggest that the effects of PD-1 blockade may be dependent on maintenance of measurable levels of cytokine producing SIV-specific CD8 T cells following ART interruption.

Table of Contents

Purpose - 1
Introduction - 1
Materials and Methods - 5
Results - 7
Discussion - 11
Table and Figures - 13
Table 1 - 13
Figure 1 - 14
Figure 2 - 15
Figure 3 - 16
Figure 4 - 17
Figure 5 - 18
Figure 6 - 19
Figure 7 - 20
Figure 8 - 21
Figure 9 - 22
References - 23

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Immunology Biology, Virology
Keyword	SIV PD-1 Blockade CD8 T Cell
Committee Chair / Thesis Advisor	Amara, Rama Rao, Emory University
Committee Members	Eisen, Arri, Emory University Cafferty, Patrick William, Emory University

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