TY - JOUR
T1 - Continuous Effector CD8+ T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population
AU - Chu, H. Hamlet
AU - Chan, Shiao Wei
AU - Gosling, John Paul
AU - Blanchard, Nicolas
AU - Tsitsiklis, Alexandra
AU - Lythe, Grant
AU - Shastri, Nilabh
AU - Molina-París, Carmen
AU - Robey, Ellen A.
N1 - Funding Information:
We thank C. Kang for generating TG6 transgenic mice, K. Taylor and I. Chou for expert technical assistance, the NIH Tetramer Core for peptide-MHC tetramers, H. Nolla and A. Valero for cell sorting, M. Jenkins (University of Minnesota), M. Prlic (Fred Hutchson Cancer Research Center), and members of the Robey Laboratory for helpful comments. This work was supported by grants from the American National Institutes of Health P01 AI065831 (E.A.R. and N.S.), R01 AI065537 and AI093132 (E.A.R.); the American Heart Association and the California Institute for Regenerative Medicine (H.H.C.); the Human Frontier Science Program (N.B.); the UK’s National Centre for Replacement, Refinement and Reduction of Animals in Research NC/K001280/1 (J.P.G.), the Leeds Fund for International Research Collaborations (G.L. and C.M.-P.), the Biotechnology and Biological Sciences Research Council BB/F003811/1 (G.L. and C.M.-P.) and BB/G023395/1 (C.M.-P.).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/7/19
Y1 - 2016/7/19
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2016.06.013
DO - 10.1016/j.immuni.2016.06.013
M3 - Article
C2 - 27421704
AN - SCOPUS:84990828267
SN - 1074-7613
VL - 45
SP - 159
EP - 171
JO - Immunity
JF - Immunity
IS - 1
ER -