PMID- 26962232
OWN - NLM
STAT- MEDLINE
DCOM- 20160816
LR  - 20240325
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 196
IP  - 8
DP  - 2016 Apr 15
TI  - Age-Associated Resident Memory CD8 T Cells in the Central Nervous System Are 
      Primed To Potentiate Inflammation after Ischemic Brain Injury.
PG  - 3318-30
LID - 10.4049/jimmunol.1502021 [doi]
AB  - Aging is associated with an increase in basal inflammation in the CNS and an 
      overall decline in cognitive function and poorer recovery following injury. 
      Growing evidence suggests that leukocyte recruitment to the CNS is also increased 
      with normal aging, but, to date, no systematic evaluation of these age-associated 
      leukocytes has been performed. In this work, the effect of aging on CNS leukocyte 
      recruitment was examined. Aging was associated with more CD45(high) leukocytes, 
      primarily composed of conventional CD8(+) T cells. These results were strain 
      independent and seen in both sexes. Intravascular labeling and immunohistology 
      revealed the presence of parenchymal CD8(+) T cells in several regions of the 
      brain, including the choroid plexus and meninges. These cells had effector memory 
      (CD44(+)CD62L(-)) and tissue-resident phenotypes and expressed markers associated 
      with TCR activation. Analysis of TCRvbeta repertoire usage suggested that entry into 
      the CNS is most likely stochastic rather than Ag driven. Correlational analyses 
      revealed a positive association between CD8 T cell numbers and decreased 
      proinflammatory function of microglia. However, the effects of cerebral ischemia 
      and ex vivo stimulation of these cells dramatically increased production of TNF, 
      IFN-gamma, and MCP-1/CCL2. Taken together, we identified a novel population of 
      resident memory, immunosurveillant CD8 T cells that represent a hallmark of CNS 
      aging and appear to modify microglia homeostasis under normal conditions, but are 
      primed to potentiate inflammation and leukocyte recruitment following ischemic 
      injury.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Ritzel, Rodney M
AU  - Ritzel RM
AD  - Neuroscience Department, University of Connecticut Health Center, Farmington, CT 
      06030;
FAU - Crapser, Joshua
AU  - Crapser J
AD  - Neuroscience Department, University of Connecticut Health Center, Farmington, CT 
      06030;
FAU - Patel, Anita R
AU  - Patel AR
AD  - Neuroscience Department, University of Connecticut Health Center, Farmington, CT 
      06030;
FAU - Verma, Rajkumer
AU  - Verma R
AD  - Neuroscience Department, University of Connecticut Health Center, Farmington, CT 
      06030;
FAU - Grenier, Jeremy M
AU  - Grenier JM
AD  - Immunology Department, University of Connecticut Health Center, Farmington, CT 
      06030; and.
FAU - Chauhan, Anjali
AU  - Chauhan A
AD  - Neuroscience Department, University of Connecticut Health Center, Farmington, CT 
      06030;
FAU - Jellison, Evan R
AU  - Jellison ER
AD  - Immunology Department, University of Connecticut Health Center, Farmington, CT 
      06030; and.
FAU - McCullough, Louise D
AU  - McCullough LD
AD  - Neuroscience Department, University of Connecticut Health Center, Farmington, CT 
      06030; Department of Neurology, McGovern Medical School, University of Texas 
      Health Science Center, Houston, TX 77370 Louise.D.McCullough@uth.tmc.edu.
LA  - eng
GR  - F31 NS083244-01A1/NS/NINDS NIH HHS/United States
GR  - R01 NS055215/NS/NINDS NIH HHS/United States
GR  - R21 NS076293/NS/NINDS NIH HHS/United States
GR  - R21 NS076293-01A1/NS/NINDS NIH HHS/United States
GR  - F31 NS083244/NS/NINDS NIH HHS/United States
GR  - R01 NS077769/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160309
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Cd44 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126880-86-2 (L-Selectin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Age Factors
MH  - Aging/*immunology
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Brain/*immunology/pathology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Chemokine CCL2/biosynthesis
MH  - Disease Models, Animal
MH  - Female
MH  - Hyaluronan Receptors/metabolism
MH  - Immunologic Memory/immunology
MH  - Immunologic Surveillance/immunology
MH  - Infarction, Middle Cerebral Artery/*immunology/pathology
MH  - Inflammation/immunology
MH  - Interferon-gamma/biosynthesis
MH  - L-Selectin/metabolism
MH  - Lymphocyte Count
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Microglia/pathology
MH  - Receptors, Antigen, T-Cell, alpha-beta/immunology
MH  - Stroke/*immunology/pathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC4868658
MID - NIHMS760161
EDAT- 2016/03/11 06:00
MHDA- 2016/08/17 06:00
PMCR- 2017/04/15
CRDT- 2016/03/11 06:00
PHST- 2015/09/16 00:00 [received]
PHST- 2016/02/05 00:00 [accepted]
PHST- 2016/03/11 06:00 [entrez]
PHST- 2016/03/11 06:00 [pubmed]
PHST- 2016/08/17 06:00 [medline]
PHST- 2017/04/15 00:00 [pmc-release]
AID - jimmunol.1502021 [pii]
AID - 10.4049/jimmunol.1502021 [doi]
PST - ppublish
SO  - J Immunol. 2016 Apr 15;196(8):3318-30. doi: 10.4049/jimmunol.1502021. Epub 2016 
      Mar 9.