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
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