Prolonged Antigen Presentation Is Required for Optimal CD8+ T Cell Responses against Malaria Liver Stage Parasites
Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization—a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.
Vyšlo v časopise:
Prolonged Antigen Presentation Is Required for Optimal CD8+ T Cell Responses against Malaria Liver Stage Parasites. PLoS Pathog 6(5): e32767. doi:10.1371/journal.ppat.1000877
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000877
Souhrn
Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization—a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.
Zdroje
1. ClydeDF
1975 Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am J Trop Med Hyg 24 397 401
2. NussenzweigRS
VanderbergJ
MostH
OrtonC
1967 Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature 216 160 162
3. SchofieldL
VillaquiranJ
FerreiraA
SchellekensH
NussenzweigR
1987 Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature 330 664 666
4. WeissWR
SedegahM
BeaudoinRL
MillerLH
GoodMF
1988 CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A 85 573 576
5. SchellerLF
AzadAF
1995 Maintenance of protective immunity against malaria by persistent hepatic parasites derived from irradiated sporozoites. Proc Natl Acad Sci U S A 92 4066 4068
6. KaechSM
AhmedR
2001 Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nat Immunol 2 415 422
7. van StipdonkMJ
LemmensEE
SchoenbergerSP
2001 Naive CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation. Nat Immunol 2 423 429
8. MercadoR
VijhS
AllenSE
KerksiekK
PilipIM
2000 Early programming of T cell populations responding to bacterial infection. J Immunol 165 6833 6839
9. BevanMJ
FinkPJ
2001 The CD8 response on autopilot. Nat Immunol 2 381 382
10. DayCL
KaufmannDE
KiepielaP
BrownJA
MoodleyES
2006 PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443 350 354
11. ZajacAJ
BlattmanJN
Murali-KrishnaK
SourdiveDJ
SureshM
1998 Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188 2205 2213
12. CallanMF
2003 The evolution of antigen-specific CD8+ T cell responses after natural primary infection of humans with Epstein-Barr virus. Viral Immunol 16 3 16
13. GillespieGM
WillsMR
AppayV
O'CallaghanC
MurphyM
2000 Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors. J Virol 74 8140 8150
14. SnyderCM
ChoKS
BonnettEL
van DommelenS
ShellamGR
2008 Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells. Immunity 29 650 659
15. VezysV
MasopustD
KemballCC
BarberDL
O'MaraLA
2006 Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med 203 2263 2269
16. Jelley-GibbsDM
BrownDM
DibbleJP
HaynesL
EatonSM
2005 Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J Exp Med 202 697 706
17. TurnerDL
CauleyLS
KhannaKM
LefrancoisL
2007 Persistent antigen presentation after acute vesicular stomatitis virus infection. J Virol 81 2039 2046
18. ZammitDJ
TurnerDL
KlonowskiKD
LefrancoisL
CauleyLS
2006 Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity 24 439 449
19. Jelley-GibbsDM
DibbleJP
BrownDM
StruttTM
McKinstryKK
2007 Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response. J Immunol 178 7563 7570
20. KhanZM
VanderbergJP
1991 Role of host cellular response in differential susceptibility of nonimmunized BALB/c mice to Plasmodium berghei and Plasmodium yoelii sporozoites. Infect Immun 59 2529 2534
21. BadovinacVP
HaringJS
HartyJT
2007 Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8(+) T cell response to infection. Immunity 26 827 841
22. PinschewerDD
OchsenbeinAF
OdermattB
BrinkmannV
HengartnerH
2000 FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J Immunol 164 5761 5770
23. ChakravartyS
CockburnIA
KukS
OverstreetMG
SacciJB
2007 CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nat Med 13 1035 1041
24. JungS
UnutmazD
WongP
SanoG
De los SantosK
2002 In vivo depletion of CD11c(+) dendritic cells abrogates priming of CD8(+) T cells by exogenous cell-associated antigens. Immunity 17 211 220
25. van RooijenN
SandersA
van den BergTK
1996 Apoptosis of macrophages induced by liposome-mediated intracellular delivery of clodronate and propamidine. J Immunol Methods 193 93 99
26. Asselin-PaturelC
BrizardG
PinJJ
BriereF
TrinchieriG
2003 Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody. J Immunol 171 6466 6477
27. AllanRS
WaithmanJ
BedouiS
JonesCM
VilladangosJA
2006 Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25 153 162
28. ChenJ
TrounstineM
AltFW
YoungF
KuraharaC
1993 Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. Int Immunol 5 647 656
29. NusslerA
FollezouJY
MiltgenF
MazierD
1989 Effect of irradiation on Plasmodium sporozoites depends on the species of hepatocyte infected. Trop Med Parasitol 40 468 469
30. SilvieO
SemblatJP
FranetichJF
HannounL
ElingW
2002 Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre-erythrocytic malaria vaccines. Parasite Immunol 24 221 223
31. SykulevY
JooM
VturinaI
TsomidesTJ
EisenHN
1996 Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response. Immunity 4 565 571
32. BerenzonD
SchwenkRJ
LetellierL
Guebre-XabierM
WilliamsJ
2003 Protracted protection to Plasmodium berghei malaria is linked to functionally and phenotypically heterogeneous liver memory CD8+ T cells. J Immunol 171 2024 2034
33. MuellerAK
DeckertM
HeissK
GoetzK
MatuschewskiK
2007 Genetically attenuated Plasmodium berghei liver stages persist and elicit sterile protection primarily via CD8 T cells. Am J Pathol 171 107 115
34. BelnoueE
CostaFT
FrankenbergT
VigarioAM
VozaT
2004 Protective T cell immunity against malaria liver stage after vaccination with live sporozoites under chloroquine treatment. J Immunol 172 2487 2495
35. HafallaJC
SanoG
CarvalhoLH
MorrotA
ZavalaF
2002 Short-term antigen presentation and single clonal burst limit the magnitude of the CD8(+) T cell responses to malaria liver stages. Proc Natl Acad Sci U S A 99 11819 11824
36. LeiriaoP
MotaMM
RodriguezA
2006 Reply to Rénia et al. The Journal of Infectious Diseases 193 164 165
37. PutriantiED
SilvieO
KordesM
BorrmannS
MatuschewskiK
2009 Vaccine-like immunity against malaria by repeated causal-prophylactic treatment of liver-stage Plasmodium parasites. J Infect Dis 199 899 903
38. TaylorWR
WhiteNJ
2004 Antimalarial drug toxicity: a review. Drug Saf 27 25 61
39. RomeroP
MaryanskiJL
CorradinG
NussenzweigRS
NussenzweigV
1989 Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature 341 323 326
40. HafallaJC
RaiU
MorrotA
Bernal-RubioD
ZavalaF
2006 Priming of CD8+ T cell responses following immunization with heat-killed Plasmodium sporozoites. Eur J Immunol 36 1179 1186
41. HaySI
RogersDJ
ToomerJF
SnowRW
2000 Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, Internet access and review. Trans R Soc Trop Med Hyg 94 113 127
42. BilsboroughJ
CarlisleM
GoodMF
1993 Identification of Caucasian CD4 T cell epitopes on the circumsporozoite protein of Plasmodium vivax. T cell memory. J Immunol 151 890 899
43. ZeveringY
KhamboonruangC
RungruengthanakitK
TungviboonchaiL
RuengpipattanapanJ
1994 Life-spans of human T-cell responses to determinants from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax. Proc Natl Acad Sci U S A 91 6118 6122
44. DoolanDL
HoffmanSL
SouthwoodS
WentworthPA
SidneyJ
1997 Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles. Immunity 7 97 112
45. CockburnIA
ChakravartyS
OverstreetMG
Garcia-SastreA
ZavalaF
2008 Memory CD8+ T cell responses expand when antigen presentation overcomes T cell self-regulation. J Immunol 180 64 71
46. KhannaKM
AguilaCC
RedmanJM
Suarez-RamirezJE
LefrancoisL
2008 In situ imaging reveals different responses by naive and memory CD8 T cells to late antigen presentation by lymph node DC after influenza virus infection. Eur J Immunol 38 3304 3315
47. ProbstHC
TschannenK
OdermattB
SchwendenerR
ZinkernagelRM
2005 Histological analysis of CD11c-DTR/GFP mice after in vivo depletion of dendritic cells. Clin Exp Immunol 141 398 404
48. BelzGT
SmithCM
KleinertL
ReadingP
BrooksA
2004 Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc Natl Acad Sci U S A 101 8670 8675
49. InabaK
TurleyS
YamaideF
IyodaT
MahnkeK
1998 Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J Exp Med 188 2163 2173
50. LeeJW
EpardaudM
SunJ
BeckerJE
ChengAC
2007 Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol 8 181 190
51. GonzalezM
MackayF
BrowningJL
Kosco-VilboisMH
NoelleRJ
1998 The sequential role of lymphotoxin and B cells in the development of splenic follicles. J Exp Med 187 997 1007
52. FuYX
HuangG
WangY
ChaplinDD
1998 B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion. J Exp Med 187 1009 1018
53. KamathAT
HenriS
BattyeF
ToughDF
ShortmanK
2002 Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100 1734 1741
54. SanoG
HafallaJC
MorrotA
AbeR
LafailleJJ
2001 Swift development of protective effector functions in naive CD8(+) T cells against malaria liver stages. J Exp Med 194 173 180
55. Bruna-RomeroO
HafallaJC
Gonzalez-AseguinolazaG
SanoG
TsujiM
2001 Detection of malaria liver-stages in mice infected through the bite of a single Anopheles mosquito using a highly sensitive real-time PCR. Int J Parasitol 31 1499 1502
56. ZammitDJ
CauleyLS
PhamQM
LefrancoisL
2005 Dendritic cells maximize the memory CD8 T cell response to infection. Immunity 22 561 570
57. MasopustD
VezysV
MarzoAL
LefrancoisL
2001 Preferential localization of effector memory cells in nonlymphoid tissue. Science 291 2413 2417
58. BarnesE
WardSM
KasprowiczVO
DusheikoG
KlenermanP
2004 Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. Eur J Immunol 34 1570 1577
59. ObarJJ
KhannaKM
LefrancoisL
2008 Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity 28 859 869
60. ScribaTJ
PurbhooM
DayCL
RobinsonN
FidlerS
2005 Ultrasensitive detection and phenotyping of CD4+ T cells with optimized HLA class II tetramer staining. J Immunol 175 6334 6343
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2010 Číslo 5
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Quorum Sensing Inhibition Selects for Virulence and Cooperation in
- The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis
- Susceptibility to Anthrax Lethal Toxin-Induced Rat Death Is Controlled by a Single Chromosome 10 Locus That Includes
- Demonstration of Cross-Protective Vaccine Immunity against an Emerging Pathogenic Ebolavirus Species