School of Medicine and Health Sciences Poster Presentations

Title

Exhaustion in Memory CD8 T Cell Subsets during Chronic Toxoplasma gondii Infection

Document Type

Poster

Abstract Category

Immunology/Infectious Diseases

Keywords

CD8 memory T cells, chronic infection, toxoplasmosis, exhaustion

Publication Date

Spring 5-1-2019

Abstract

Toxoplasmosis is an infectious disease caused by apicomplexa parasite Toxoplasma gondii (T. gondii). According to the Centers for Disease and Control (CDC), toxoplasmosis is one of the leading causes of mortality among foodborne diseases in the United States. Cell-mediated immune response to toxoplasma gondii infection is critically related with CD8 T lymphocyte cells. However, due to over expression of inhibitory receptors, CD8 T cells ultimately lose their functionality which is manifested by decrease in their cytokine producing ability and other effector mechanisms. This stage is referred to as “state of T cell exhaustion”, and it results in the decreased host ability to prevent optimal control of infection. Recent studies from our laboratory have demonstrated that during chronic toxoplasmosis, CD8 memory T cells exhibit a progressive loss of polyfunctionality accompanied with elevated expression level of programmed cell death protein 1 (PD-1). CD8 memory T cell response, which is comprised of central memory T cells (Tcm) and effector memory T cells (Tem), will be further investigated during the early chronic phase (Week 5-6 post-infection (p.i.)) and late chronic phase (Week 7-8 p.i.) of the infection. C57BL/6 mice infected with 10 cysts of Me49 strain of T. gondii via oral gavage, were sacrificed at week 5 and week 8 p.i.. Toxoplasma specific CD8 Tcm (CD62L+CCR7+) and Tem (CD62L-CCR7-) were analyzed by multicolor flow cytometry analysis. Antigen specific splenic CD8 T cells were defined using a previously published surrogate marker strategy (CD44hiCD11ahi). Flow cytometry analysis revealed an increased expression of multiple inhibitory markers associated with T cells exhaustion, including PD-1, Tim-3, TIGIT, 2B4, CTLA-4, and Lag-3 on both CD8 Tcm and Tem at week 8 p.i.. However, CD8 Tcm exhibited higher expression of all inhibitory markers compared to Tem which is correlated with a loss of functionality.

Open Access

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Presented at Research Days 2019.

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Exhaustion in Memory CD8 T Cell Subsets during Chronic Toxoplasma gondii Infection

Toxoplasmosis is an infectious disease caused by apicomplexa parasite Toxoplasma gondii (T. gondii). According to the Centers for Disease and Control (CDC), toxoplasmosis is one of the leading causes of mortality among foodborne diseases in the United States. Cell-mediated immune response to toxoplasma gondii infection is critically related with CD8 T lymphocyte cells. However, due to over expression of inhibitory receptors, CD8 T cells ultimately lose their functionality which is manifested by decrease in their cytokine producing ability and other effector mechanisms. This stage is referred to as “state of T cell exhaustion”, and it results in the decreased host ability to prevent optimal control of infection. Recent studies from our laboratory have demonstrated that during chronic toxoplasmosis, CD8 memory T cells exhibit a progressive loss of polyfunctionality accompanied with elevated expression level of programmed cell death protein 1 (PD-1). CD8 memory T cell response, which is comprised of central memory T cells (Tcm) and effector memory T cells (Tem), will be further investigated during the early chronic phase (Week 5-6 post-infection (p.i.)) and late chronic phase (Week 7-8 p.i.) of the infection. C57BL/6 mice infected with 10 cysts of Me49 strain of T. gondii via oral gavage, were sacrificed at week 5 and week 8 p.i.. Toxoplasma specific CD8 Tcm (CD62L+CCR7+) and Tem (CD62L-CCR7-) were analyzed by multicolor flow cytometry analysis. Antigen specific splenic CD8 T cells were defined using a previously published surrogate marker strategy (CD44hiCD11ahi). Flow cytometry analysis revealed an increased expression of multiple inhibitory markers associated with T cells exhaustion, including PD-1, Tim-3, TIGIT, 2B4, CTLA-4, and Lag-3 on both CD8 Tcm and Tem at week 8 p.i.. However, CD8 Tcm exhibited higher expression of all inhibitory markers compared to Tem which is correlated with a loss of functionality.