School of Medicine and Health Sciences Poster Presentations
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
1
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.
Comments
Presented at Research Days 2019.