Continuous Effector CD8+ T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population

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Highly functional CD8+ effector T (Teff) cells can persist in large numbers during controlled persistent infections, as exemplified by rare HIV-infected individuals who control the virus. Here we examined the cellular mechanisms that maintain ongoing T effector responses using a mouse model for persistent Toxoplasma gondii infection. In mice expressing the protective MHC-I molecule, H-2Ld, a dominant T effector response against a single parasite antigen was maintained without a contraction phase, correlating with ongoing presentation of the dominant antigen. Large numbers of short-lived Teff cells were continuously produced via a proliferative, antigen-dependent intermediate (Tint) population with a memory-effector hybrid phenotype. During an acute, resolved infection, decreasing antigen load correlated with a sharp drop in the Tint cell population and subsequent loss of the ongoing effector response. Vaccination approaches aimed at the development of Tint populations might prove effective against pathogens that lead to chronic infection.

Chu et al. show that ongoing presentation of an immunodominant pathogen-derived antigen sustains a proliferative CD8+ T cell subset with a phenotype that combines features of memory and effector T cells, thus revealing the source of functional CD8+ effector T cells that control persistent infections. This intermediate subset continuously generates short-lived effector T cells and contributes to memory and effector T cell homeostasis.

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