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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2016 Jul 17

PMID 27421704

Citations 49

Authors

H Hamlet Chu

Shiao-Wei Chan

John Paul Gosling

Nicolas Blanchard

Alexandra Tsitsiklis

Grant Lythe

Nilabh Shastri

Carmen Molina-Paris

Ellen A Robey

Affiliations

Soon will be listed here.

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.

Citing Articles

Comparative analysis of changes in immune cell in the chicken spleen across different ages using flow cytometry.

Lee Y, Lee R, Kim J, Han Y, Hunter C, Park J BMC Vet Res. 2024; 20(1):429.

PMID: 39334332 PMC: 11438354. DOI: 10.1186/s12917-024-04287-2.

Protective function and differentiation cues of brain-resident CD8+ T cells during surveillance of latent infection.

Porte R, Belloy M, Audibert A, Bassot E, Aida A, Alis M Proc Natl Acad Sci U S A. 2024; 121(24):e2403054121.

PMID: 38838017 PMC: 11181119. DOI: 10.1073/pnas.2403054121.

Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity.

Tu T, Grunbaum A, Santinon F, Kazanova A, Rozza N, Kremer R Commun Biol. 2024; 7(1):526.

PMID: 38702425 PMC: 11068881. DOI: 10.1038/s42003-024-05922-2.

Endogenous IL-27 during toxoplasmosis limits early monocyte responses and their inflammatory activation by pathological T cells.

Aldridge D, Moodley D, Park J, Phan A, Rausch M, White K mBio. 2024; 15(3):e0008324.

PMID: 38376210 PMC: 10936422. DOI: 10.1128/mbio.00083-24.

Short chain fatty acids facilitate protective immunity by macrophages and T cells during acute fowl adenovirus-4 infection.

Lee R, Yoon B, Hunter C, Kwon H, Sung H, Park J Sci Rep. 2023; 13(1):17999.

PMID: 37865711 PMC: 10590440. DOI: 10.1038/s41598-023-45340-8.

References

Paley M, Kroy D, Odorizzi P, Johnnidis J, Dolfi D, Barnett B . Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science. 2012; 338(6111):1220-5. PMC: 3653769. DOI: 10.1126/science.1229620. View

Jameson S, Masopust D . Diversity in T cell memory: an embarrassment of riches. Immunity. 2010; 31(6):859-71. PMC: 2957815. DOI: 10.1016/j.immuni.2009.11.007. View

Nelson R, McLachlan J, Kurtz J, Jenkins M . CD4+ T cell persistence and function after infection are maintained by low-level peptide:MHC class II presentation. J Immunol. 2013; 190(6):2828-34. PMC: 3594488. DOI: 10.4049/jimmunol.1202183. View

Snyder C, Cho K, Bonnett E, Allan J, Hill A . Sustained CD8+ T cell memory inflation after infection with a single-cycle cytomegalovirus. PLoS Pathog. 2011; 7(10):e1002295. PMC: 3188546. DOI: 10.1371/journal.ppat.1002295. View

Torti N, Walton S, Brocker T, Rulicke T, Oxenius A . Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection. PLoS Pathog. 2011; 7(10):e1002313. PMC: 3203160. DOI: 10.1371/journal.ppat.1002313. View

Kosmrlj A, Read E, Qi Y, Allen T, Altfeld M, Deeks S . Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature. 2010; 465(7296):350-4. PMC: 3098720. DOI: 10.1038/nature08997. View

Simonetta F, Hua S, Lecuroux C, Gerard S, Boufassa F, Saez-Cirion A . High eomesodermin expression among CD57+ CD8+ T cells identifies a CD8+ T cell subset associated with viral control during chronic human immunodeficiency virus infection. J Virol. 2014; 88(20):11861-71. PMC: 4178742. DOI: 10.1128/JVI.02013-14. View

Ferguson D, HUTCHISON W, Pettersen E . Tissue cyst rupture in mice chronically infected with Toxoplasma gondii. An immunocytochemical and ultrastructural study. Parasitol Res. 1989; 75(8):599-603. DOI: 10.1007/BF00930955. View

Karrer U, Sierro S, Wagner M, Oxenius A, Hengel H, Koszinowski U . Memory inflation: continuous accumulation of antiviral CD8+ T cells over time. J Immunol. 2003; 170(4):2022-9. DOI: 10.4049/jimmunol.170.4.2022. View

10.

Almeida J, Price D, Papagno L, Arkoub Z, Sauce D, Bornstein E . Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med. 2007; 204(10):2473-85. PMC: 2118466. DOI: 10.1084/jem.20070784. View

11.

Feliu V, Vasseur V, Grover H, Chu H, Brown M, Wang J . Location of the CD8 T cell epitope within the antigenic precursor determines immunogenicity and protection against the Toxoplasma gondii parasite. PLoS Pathog. 2013; 9(6):e1003449. PMC: 3688528. DOI: 10.1371/journal.ppat.1003449. View

12.

Hiramoto R, Galisteo A, Nascimento N, de Andrade Jr H . 200 Gy sterilised Toxoplasma gondii tachyzoites maintain metabolic functions and mammalian cell invasion, eliciting cellular immunity and cytokine response similar to natural infection in mice. Vaccine. 2002; 20(16):2072-81. DOI: 10.1016/s0264-410x(02)00054-3. View

13.

Zehn D, Lee S, Bevan M . Complete but curtailed T-cell response to very low-affinity antigen. Nature. 2009; 458(7235):211-4. PMC: 2735344. DOI: 10.1038/nature07657. View

14.

Montoya J, Liesenfeld O . Toxoplasmosis. Lancet. 2004; 363(9425):1965-76. DOI: 10.1016/S0140-6736(04)16412-X. View

15.

Wherry E . T cell exhaustion. Nat Immunol. 2011; 12(6):492-9. DOI: 10.1038/ni.2035. View

16.

Vidal S, Lanier L . NK cell recognition of mouse cytomegalovirus-infected cells. Curr Top Microbiol Immunol. 2005; 298:183-206. DOI: 10.1007/3-540-27743-9_10. View

17.

Graef P, Buchholz V, Stemberger C, Flossdorf M, Henkel L, Schiemann M . Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells. Immunity. 2014; 41(1):116-26. DOI: 10.1016/j.immuni.2014.05.018. View

18.

Virgin H, Wherry E, Ahmed R . Redefining chronic viral infection. Cell. 2009; 138(1):30-50. DOI: 10.1016/j.cell.2009.06.036. View

19.

Intlekofer A, Takemoto N, Wherry E, Longworth S, Northrup J, Palanivel V . Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol. 2005; 6(12):1236-44. DOI: 10.1038/ni1268. View

20.

Bhadra R, Gigley J, Weiss L, Khan I . Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade. Proc Natl Acad Sci U S A. 2011; 108(22):9196-201. PMC: 3107287. DOI: 10.1073/pnas.1015298108. View