학술논문

Continuous Effector CD8+ T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population
Document Type
article
Source
Immunity. 45(1)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Immunology
Prevention
HIV/AIDS
Infectious Diseases
Emerging Infectious Diseases
Immunization
Vaccine Related
Biodefense
2.1 Biological and endogenous factors
Aetiology
Inflammatory and immune system
Infection
Animals
Antigen Presentation
Antigens
Protozoan
CD8-Positive T-Lymphocytes
Cell Differentiation
Cell Proliferation
Cells
Cultured
Chronic Disease
Cytotoxicity
Immunologic
Histocompatibility Antigens Class I
Immunodominant Epitopes
Immunologic Memory
Lymphocyte Subsets
Mice
Mice
Inbred BALB C
Mice
Inbred C57BL
Mice
Transgenic
Receptors
Antigen
T-Cell
Toxoplasma
Toxoplasmosis
Language
Abstract
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-2L(d), 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.