CD4 and IL-2 mediated NK cell responses after COVID-19 infection and mRNA vaccination in adults

Amir M. Alhajjat*, Catherine R. Redden, Morgan Langereis, Steven T. Papastefan, Joy A.S. Ito, Katherine C. Ott, Lucas E. Turner, Hee Kap K. Kang, Aimen F. Shaaban

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


A detailed understanding of protective immunity against SARS-CoV-2 is incredibly important in fighting the pandemic. Central to protective immunity is the ability of the immune system to recall previous exposures. Although antibody and T cell immunity have gained considerable attention, the contribution of the NK cell compartment to immune recall and protection from SARS-CoV-2 has not been explored. In this study, we investigate the NK cell responses to stimulation with SARS-CoV-2 in previously exposed and non-exposed individuals. We show that NK cells demonstrate an enhanced CD4+ T cell dependent response when re-exposed to SARS-CoV-2 antigen. The enhanced response is dependent on T cells and correlates with the number of SARS-CoV-2 specific CD4 T cells. We find that IL-2 is a critical mediator of NK cell function. These findings suggest that NK cells contribute to the protective responses against SARS-CoV-2 through a cooperation with antigen-specific CD4 T cells and have significant implications on our understanding of protective immunity in SARS-CoV-2.

Original languageEnglish (US)
Article number152304
Issue number1
StatePublished - Jan 2023


  • Adaptive immunity
  • BNT162b2
  • CD4
  • COVID-19
  • IL-2
  • Memory
  • NK cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology


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