Suppressive CD8+ T-Cells Are Key Cellular Mediators of Extracorporeal Photopheresis

Kai J Rogers; Kathryn L Eschbacher; Zeb Zacharias; Kshitija Kale; Michael P Crawford; Charles Michael Knudson; Alexander W Boyden; Nitin J Karandikar

doi:10.1002/jca.70094

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Suppressive CD8+ T-Cells Are Key Cellular Mediators of Extracorporeal Photopheresis

Journal article

Open access

Peer reviewed

Suppressive CD8+ T-Cells Are Key Cellular Mediators of Extracorporeal Photopheresis

Kai J Rogers, Kathryn L Eschbacher, Zeb Zacharias, Kshitija Kale, Michael P Crawford, Charles Michael Knudson, Alexander W Boyden and Nitin J Karandikar

Journal of clinical apheresis, Vol.41(1), e70094

02/01/2026

DOI: 10.1002/jca.70094

PMCID: PMC12882035

PMID: 41653030

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https://doi.org/10.1002/jca.70094View

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Abstract

Extracorporeal photopheresis (ECP) is a widely utilized immunomodulatory procedure with an incompletely defined mechanism. In graft-versus-host disease (GvHD) and transplant rejection, ECP is thought to induce immune tolerance by increasing regulatory CD4+ T-cells, whereas in cutaneous T cell lymphoa it may enhance dendritic cell-mediated antigen presentation and cytotoxic T cell activity. We investigated the role of CD8+ T cells in ECP using a murine model of multiple sclerosis (MS). ECP protected mice from disease, mitigated CNS pathology, and was dependent on CD8+ T cells. Translation to patients revealed increased numbers of suppressive CD8+ T-cells. Functional assays identified enhanced suppressive capacity of CD8+ T-cells in ECP patients and longitudinal studies found this occurred within 1 month of starting ECP. Using both a murine model and clinical samples, our findings reveal a mechanistic role for suppressive CD8+ T-cells in mediating the effects of ECP, potentially providing a unifying mechanism for ECP's apparently dichotomous effects.

Animals

CD8-Positive T-Lymphocytes - immunology

Disease Models, Animal

Female

Graft vs Host Disease

Humans

Immune Tolerance

Male

Mice

Mice, Inbred C57BL

Multiple Sclerosis - immunology

Multiple Sclerosis - therapy

Photopheresis - methods

Details

Title: Subtitle: Suppressive CD8+ T-Cells Are Key Cellular Mediators of Extracorporeal Photopheresis
Creators: Kai J Rogers - University of Iowa
Kathryn L Eschbacher - University of Iowa
Zeb Zacharias - University of Iowa Health Care
Kshitija Kale - University of Iowa
Michael P Crawford - University of Iowa
Charles Michael Knudson - University of Iowa Health Care
Alexander W Boyden - University of Iowa
Nitin J Karandikar - Veterans Health Administration
Resource Type: Journal article
Publication Details: Journal of clinical apheresis, Vol.41(1), e70094
DOI: 10.1002/jca.70094
PMID: 41653030
PMCID: PMC12882035
NLM abbreviation: J Clin Apher
ISSN: 0733-2459
eISSN: 1098-1101
Publisher: Wiley
Grant note: 5UE5NS079173 / NIH HHS P30CA086862 / NIH HHS I01CX002319 / U.S. Department of Veterans Affairs I01BX003677 / U.S. Department of Veterans Affairs
Language: English
Date published: 02/01/2026
Academic Unit: Pathology; Holden Comprehensive Cancer Center
Record Identifier: 9985139491102771

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