Effect of intranasal 33C temperature on NK and ADCC activities 3462

Abstract Description Several coronaviruses cause common colds and replicate more efficiently at the intranasal temperature (33C) vs. body temperature (37C). These infections can be mitigated by immune mechanisms, including natural killer (NK) cell activity and NK antibody-dependent cell-mediated cytotoxicity (ADCC). This study investigated whether lower temperatures decreased NK and ADCC killing using NK-92-CD16A cells, CD20+ Daudi B cells (51Cr-labeled), and anti-CD20 mAbs: rituximab-biosimilar and GA101 WT. Changes in cytotoxicity were monitored using (1) the effective antibody concentrations needed for 50% ADCC (EC50s) and (2) lytic units (LU/1M NK) cells were used to determine if more NK cells were required to support lysis at 33C. Results showed far greater NK killing at 37C. Rituximab showed little change for EC50 and lytic units while GA101 mAb showed a ∼3-fold difference in EC50 at 33C vs. 37C and decreased LU/M. GA101 data indicated that more antibodies and additional NK cells are necessary for cytotoxicity at lower temperatures. Although the mAbs bind to overlapping epitopes, they differ. Type 1 anti-CD20 rituximab enters lipid rafts (and binds 2X better) than type 2 anti-CD20 GA101. We conclude that the lower temperature 33C significantly reduces NK and can reduce ADCC. These findings reveal the impact of intranasal temperatures on immune mechanisms, particularly initial NK and secondary ADCC responses that are important to control respiratory infections. Funding Sources 5T34GM145539-03; University of Nevada, Reno Foundation Topic Categories Mucosal and Regional Immunology (MUC)