CD8 memory subset response in encephalitis model of Toxoplasma gondii infection:
Magali Moretto, Keer Chen, Christina Cox, Jie Chen, and Imtiaz A Khan
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC.
CD8 T cells play an important role in protection against Toxoplasma gondii, especially during the chronic phase of infection. Due to the ability of these cells to exhibit polyfunctional response including IFNg production and cytotoxic effect, the parasitic replication is kept under control. However, in an encephalitis model of infection, it has been demonstrated that memory CD8 T cells become exhausted due to an increased expression of inhibitory receptors like PD-1 that leads to reactivation of infection and host mortality. While studies performed with chronic viral infections and tumor models have reported that CD8 T cell memory is comprised of a heterogeneous population, in-depth information related to this response against T. gondii infection is scarce. We observed that after T. gondii infection, memory CD8 T cells do not fit into classical effector and memory phenotype but can be distributed into four subsets based on KLRG1 and CD62L expression. KLRG1+CD62L- CD8 T cell subset (pop1) displays the classical attribute of effector T cells while the 3 remaining subsets KLRG1-CD62L– (pop2), KLRG1-CD62L+ (pop3) and KLRG1+CD62L+ (pop4) exhibit higher CD127 expression, a characteristic of memory population signature. Interestingly, pop3 and 4 exhibit increased levels of multiple inhibitory receptors. Adoptive transfer studies suggest that the effector population (pop1), needed for controlling infection, is derived from pop3 that displays stem-like characteristics, with pop4 most likely acting as the intermediate population. These observations suggest that pop3 needs to be efficiently maintained to generate highly polyfunctional pop1 effectors to keep the chronic infection under control.