Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients
Kenichi Ishiyama, Janice Arakawa‐Hoyt, Oscar A. Aguilar, Izabella Damm, Parhom Towfighi, Tara K. Sigdel, Stanley Tamaki, Joël Babdor, Matthew H. Spitzer, Elaine F. Reed, Minnie Sarwal, Lewis L. Lanier, CMV Systems Immunobiology Group, Kenichi Ishiyama, Janice Arakawa‐Hoyt, Tara K. Sigdel, Elaine F. Reed, Minnie M. Sarwal, Lewis L. Lanier, Richard Ahn, Jenny Brook, Suphamai Bunnapradist, Nakul Datta, Mario C. Deng, Don J. Diamond, Tin Doung, Janette Gadzhyan, David Elashoff, David W. Gjertson, Victoria Groysberg, Alexander F. Hoffman, Erik L. Lum, Harry Pickering, Z. Qian, Michelle Ramírez, Maura Rossetti, Dimitri Rychov, Joanna Schaenman, Andrew Schroeder, Subha Sen, Danielle Sim, Marina Sirota, Flavio Vicenti, Otto O. Yang
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.