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W147 - Trajectories of Immune Aging in Diverse Adults Reveal an Immunosenescent Cytotoxic NK Cell Population

Wednesday, June 21, 2023

7:30 AM – 7:30 PM

masashi Fujita – Senior Research Associate, 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Tain Luquez – PhD student, 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Annie Lee – Assistant Professor, 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Joshua Gray – Post-Doc, 2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; christian Habeck – Assistant Professor, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.; Leah Zuroff – Neurology Resident, 3Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (CNET), Perelman School of Medicine, University of Pennsylvania, Philadelphia PA USA; Adam Brickman – Professor, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.; Donna Farber – Professor, Columbi2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Amit Bar-Or – Professor, The University Of Pennsylvania3Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (CNET), Perelman School of Medicine, University of Pennsylvania, Philadelphia PA USA; Yaakov Stern – Professor, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York; Philip De Jager – Professor, Neurology, 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA, Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA

HT

Hanane Touil, Ph.D.

postdoctoral fellow
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
New York, New York, United States
mF

masashi Fujita, Dr,

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
TL

Tain Luquez

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
AL

Annie J. Lee

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
JG

Joshua Gray

2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA
cH

christian Habeck

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
LZ

Leah Zuroff

3Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (CNET), Perelman School of Medicine, University of Pennsylvania, Philadelphia PA USA
AB

Adam Brickman

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
DF

Donna Farber

Columbi2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA
AB

Amit Bar-Or, MD

The University Of Pennsylvania3Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (CNET), Perelman School of Medicine, University of Pennsylvania, Philadelphia PA USA
YS

Yaakov Stern

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York
PD

Philip L. De Jager, MD, PhD

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA, Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA
mF

masashi Fujita, Dr,

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
TL

Tain Luquez

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
AL

Annie J. Lee

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
JG

Joshua Gray

2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA
cH

christian Habeck

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
LZ

Leah Zuroff

3Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (CNET), Perelman School of Medicine, University of Pennsylvania, Philadelphia PA USA
AB

Adam Brickman

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
DF

Donna Farber

Columbi2Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA
AB

Amit Bar-Or, MD

The University Of Pennsylvania3Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (CNET), Perelman School of Medicine, University of Pennsylvania, Philadelphia PA USA
YS

Yaakov Stern

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York
PD

Philip L. De Jager, MD, PhD

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA, Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA

Abstract Text: Immunosenescence (ISC) involves gradual changes in immune-system composition and function with advancing age. Clear multi-modal ISC trajectories remain unknown due to the limited number of large-scale studies that are mostly centered on individuals of European ancestry. Here, we examined age-associated phenotypic and functional changes of peripheral blood (n=257, age: 25-88 years) profiling participants of diverse ancestries, using multiparametric-cytometry profiles.

First, we used PhenoGraph to empirically cluster PBMCs into 38 PBMC and 43 T-cell discrete clusters. We used linear regression adjusted for sex and genetic ancestry to identify age-associated clusters. We also created an immunological-age estimate using an elastic net regression, selecting for informative cell-populations.

We report a novel CD56+PD-L1+GranzymeB+NK cell-subset increasing in frequency with age (p=0.0025). Moreover, we uncovered 10 cell-subsets newly associated with advancing age: naïve CD20+CD4+ (p=0.0028) and CD20+CD8+ (p=0,0032) T-cells, activated IgDlowCD4 central memory T-cells (p=0.0079) across all three populations. We confirmed previous findings: decreased naïve CD8 T-cells (p=5.56 x10-16), increased CD8 TEMRAs (p=3.97x10-9), decreased CD20+ B-cells (p=2.95x10-3) mostly reported in Hispanics and non-hispanic whites (NHW) with only naïve and TEMRA changes being significant in African Americans. Using these data, our estimate of the immunological-age captured 58.4% of variance in chronological-age, and it appears to be related to brain atrophy on MRI.

These findings shed light on ISC trajectories in diverse populations, which include novel ISC cytotoxic CD56+PD-L1+GranzymeB+ NK-cells, potentially contributing to higher cancer incidence in elderly. Establishing a robust immunological age measure in diverse populations will contribute to an ongoing effort to personalize immunotherapies.