Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients

Author:

Ishiyama Kenichi12ORCID,Arakawa-Hoyt Janice12,Aguilar Oscar A.12,Damm Izabella3,Towfighi Parhom3,Sigdel Tara3,Tamaki Stanley4,Babdor Joel125,Spitzer Matthew H.1256,Reed Elaine F.7,Sarwal Minnie M.3,Lanier Lewis L.12ORCID,Ishiyama Kenichi,Arakawa-Hoyt Janice,Sigdel Tara,Reed Elaine F.,Sarwal Minnie M.,Lanier Lewis L.,Ahn Richard,Brook Jenny,Bunnapradist Suphamai,Datta Nakul,Deng Mario,Diamond Don,Doung Tin,Gadzhyan Janette,Elashoff David,Gjertson David,Groysberg Victoria,Hoffman Alexander,Lum Erik,Pickering Harry,Qian Zach,Ramirez Michelle,Rossetti Maura,Rychov Dimitri,Schaenman Joanna,Schroeder Andrew,Sen Subha,Sim Danielle,Sirota Marina,Vicenti Flavio,Yang Otto,

Affiliation:

1. Department of Microbiology and Immunology, University of California, San Francisco, CA 94143

2. Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143

3. Department of Surgery, University of California, San Francisco, CA 94143

4. Parnassus Flow Cytometry Core, University of California, San Francisco, CA 94143

5. Department of Otolaryngology–Head and Neck Surgery, University of California, San Francisco, CA 94143

6. Chan Zuckerberg Biohub, San Francisco, CA 94158

7. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095

Abstract

Significance Memory-like NK cells (NKG2C + CD57 + FcεRIγ ) are established during CMV infection. Here, mass cytometry tracked the in vivo kinetics of CMV-induced memory NK cells generation and identified a unique subset of NKG2C + CD57 + FcεRIγ low–dim as potentially prememory-like NK cells in CMV-infected kidney transplant patients. The study demonstrated that prememory-like NK cells with a high cytotoxic profile proliferate along with accumulation of new memory-like NK cells, whereas preexisting memory-like NK cells decreased in the peripheral blood after transplantation. Moreover, NKG2C + CD8 + T cells and cytotoxic γδ T cells also expand during CMV infection. This interplay of three different cytotoxic lymphocytes demonstrates a combinatorial immune response against CMV infection, which may contribute to preventing CMV-associated complication in organ transplantation.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | NIH Office of the Director

Uehara Memorial Foundation

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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