PMID- 20574442
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20211028
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 130
IP  - 11
DP  - 2010 Nov
TI  - Vaccination with TAT-antigen fusion protein induces protective, CD8(+) T 
      cell-mediated immunity against Leishmania major.
PG  - 2602-10
LID - 10.1038/jid.2010.171 [doi]
AB  - In murine leishmaniasis, healing is mediated by IFN-gamma-producing CD4(+) and CD8(+) 
      T cells. Thus, an efficacious vaccine should induce Th1 and Tc1 cells. Dendritic 
      cells (DCs) pulsed with exogenous proteins primarily induce strong CD4-dependent 
      immunity; induction of CD8 responses has proven to be difficult. We evaluated the 
      immunogenicity of fusion proteins comprising the protein transduction domain of 
      HIV-1 TAT and the Leishmania antigen LACK (Leishmania homolog of receptors for 
      activated C kinase), as TAT-fusion proteins facilitate major histocompatibility 
      complex class I-dependent antigen presentation. In vitro, TAT-LACK-pulsed DCs 
      induced stronger proliferation of Leishmania-specific CD8(+) T cells compared 
      with DCs incubated with LACK alone. Vaccination with TAT-LACK-pulsed DCs or 
      fusion proteins plus adjuvant in vivo significantly improved disease outcome in 
      Leishmania major-infected mice and was superior to vaccination with DCs treated 
      with LACK alone. Vaccination with DC+TAT-LACK resulted in stronger proliferation 
      of CD8(+) T cells when compared with immunization with DC+LACK. Upon depletion of 
      CD4(+) or CD8(+) T cells, TAT-LACK-mediated protection was lost. TAT-LACK-pulsed 
      IL-12p40-deficient DCs did not promote protection in vivo. In summary, these data 
      show that TAT-fusion proteins are superior in activating Leishmania-specific Tc1 
      cells when compared with antigen alone and suggest that IL-12-dependent 
      preferential induction of antigen-specific CD8(+) cells promotes significant 
      protection against this important human pathogen.
FAU - Kronenberg, Katharina
AU  - Kronenberg K
AD  - Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
FAU - Brosch, Sven
AU  - Brosch S
FAU - Butsch, Florian
AU  - Butsch F
FAU - Tada, Yayoi
AU  - Tada Y
FAU - Shibagaki, Naotaka
AU  - Shibagaki N
FAU - Udey, Mark C
AU  - Udey MC
FAU - von Stebut, Esther
AU  - von Stebut E
LA  - eng
GR  - Z01 BC010976/ImNIH/Intramural NIH HHS/United States
GR  - Z01 SC003669/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100624
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Protozoan Vaccines)
RN  - 0 (Viral Fusion Proteins)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 163832-69-7 (LACK antigen, Leishmania)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Antigens, Protozoan/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Dendritic Cells/immunology
MH  - Interleukin-12/immunology
MH  - Leishmania major/*immunology
MH  - Leishmaniasis, Cutaneous/*immunology/*prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Protozoan Proteins/immunology
MH  - Protozoan Vaccines/*immunology
MH  - Th1 Cells/immunology
MH  - Viral Fusion Proteins/immunology
MH  - tat Gene Products, Human Immunodeficiency Virus/*immunology
PMC - PMC6999697
MID - NIHMS1067651
COIS- CONFLICT OF INTEREST The authors state no conflict of interest.
EDAT- 2010/06/25 06:00
MHDA- 2010/11/17 06:00
PMCR- 2020/02/04
CRDT- 2010/06/25 06:00
PHST- 2010/06/25 06:00 [entrez]
PHST- 2010/06/25 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
PHST- 2020/02/04 00:00 [pmc-release]
AID - S0022-202X(15)34613-3 [pii]
AID - 10.1038/jid.2010.171 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2010 Nov;130(11):2602-10. doi: 10.1038/jid.2010.171. Epub 2010 
      Jun 24.