PMID- 21098225
OWN - NLM
STAT- MEDLINE
DCOM- 20110127
LR  - 20211203
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 186
IP  - 1
DP  - 2011 Jan 1
TI  - A marked reduction in priming of cytotoxic CD8+ T cells mediated by 
      stress-induced glucocorticoids involves multiple deficiencies in 
      cross-presentation by dendritic cells.
PG  - 183-94
LID - 10.4049/jimmunol.1001737 [doi]
AB  - Protracted psychological stress elevates circulating glucocorticoids, which can 
      suppress CD8(+) T cell-mediated immunity, but the mechanisms are incompletely 
      understood. Dendritic cells (DCs), required for initiating CTL responses, are 
      vulnerable to stress/corticosterone, which can contribute to diminished CTL 
      responses. Cross-priming of CD8(+) T cells by DCs is required for initiating CTL 
      responses against many intracellular pathogens that do not infect DCs. We 
      examined the effects of stress/corticosterone on MHC class I (MHC I) 
      cross-presentation and priming and show that stress/corticosterone-exposed DCs 
      have a reduced ability to cross-present OVA and activate MHC 
      I-OVA(257-264)-specific T cells. Using a murine model of psychological stress and 
      OVA-loaded beta(2)-microglobulin knockout "donor" cells that cannot present Ag, DCs 
      from stressed mice induced markedly less Ag-specific CTL proliferation in a 
      glucocorticoid receptor-dependent manner, and endogenous in vivo T cell cytolytic 
      activity generated by cross-presented Ag was greatly diminished. These deficits 
      in cross-presentation/priming were not due to altered Ag donation, Ag uptake 
      (phagocytosis, receptor-mediated endocytosis, or fluid-phase uptake), or 
      costimulatory molecule expression by DCs. However, proteasome activity in 
      corticosterone-treated DCs or splenic DCs from stressed mice was partially 
      suppressed, which limits formation of antigenic peptide-MHC I complexes. In 
      addition, the lymphoid tissue-resident CD11b(-)CD24(+)CD8alpha(+) DC subset, which 
      carries out cross-presentation/priming, was preferentially depleted in stressed 
      mice. At the same time, CD11b(-)CD24(+)CD8alpha(-) DC precursors were increased, 
      suggesting a block in development of CD8alpha(+) DCs. Therefore, 
      glucocorticoid-induced changes in both the cellular composition of the immune 
      system and intracellular protein degradation contribute to impaired CTL priming 
      in stressed mice.
FAU - Hunzeker, John T
AU  - Hunzeker JT
AD  - Department of Microbiology and Immunology, College of Medicine, Pennsylvania 
      State University, Hershey, PA 17033, USA.
FAU - Elftman, Michael D
AU  - Elftman MD
FAU - Mellinger, Jennifer C
AU  - Mellinger JC
FAU - Princiotta, Michael F
AU  - Princiotta MF
FAU - Bonneau, Robert H
AU  - Bonneau RH
FAU - Truckenmiller, Mary E
AU  - Truckenmiller ME
FAU - Norbury, Christopher C
AU  - Norbury CC
LA  - eng
GR  - R01 AI070537/AI/NIAID NIH HHS/United States
GR  - AI065702/AI/NIAID NIH HHS/United States
GR  - R56 AI056094/AI/NIAID NIH HHS/United States
GR  - T32 CA060395/CA/NCI NIH HHS/United States
GR  - R01 AI065702/AI/NIAID NIH HHS/United States
GR  - R01 AI056094/AI/NIAID NIH HHS/United States
GR  - AI056094/AI/NIAID NIH HHS/United States
GR  - 2 T32 CA60395/CA/NCI NIH HHS/United States
GR  - C06 RR015428/RR/NCRR NIH HHS/United States
GR  - C06 RR-15428/RR/NCRR NIH HHS/United States
GR  - AI070537/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101122
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 9006-59-1 (Ovalbumin)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Corticosterone/biosynthesis/*physiology
MH  - Cross-Priming/drug effects/*immunology
MH  - Cytotoxicity, Immunologic/*drug effects/immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Immobilization
MH  - *Immunosuppression Therapy
MH  - Lymphocyte Activation/*drug effects/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Ovalbumin/immunology/metabolism
MH  - Stress, Psychological/*immunology
MH  - T-Lymphocytes, Cytotoxic/cytology/*immunology/metabolism
PMC - PMC3701459
MID - NIHMS435180
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2010/11/26 06:00
MHDA- 2011/01/29 06:00
PMCR- 2013/07/04
CRDT- 2010/11/25 06:00
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/01/29 06:00 [medline]
PHST- 2013/07/04 00:00 [pmc-release]
AID - jimmunol.1001737 [pii]
AID - 10.4049/jimmunol.1001737 [doi]
PST - ppublish
SO  - J Immunol. 2011 Jan 1;186(1):183-94. doi: 10.4049/jimmunol.1001737. Epub 2010 Nov 
      22.