1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
2. Present addresses: Emory Vaccine Center and the Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA (J.J.) and California Institute of Technology, Pasadena, California 91125, USA (D.B.).

Correspondence to: David Baltimore¹ Correspondence and requests for materials should be addressed to D.B. (e-mail: Email: baltimo@caltech.edu).

Abstract

Immunological memory is the ability of the immune system to respond with enhanced vigour to pathogens that have been encountered in the past. Following infection or immunization, most effector T cells undergo apoptotic cell death, but a small fraction of these cells, proportional to the early antigen load and initial clonal burst size¹, persist in the host as a stable pool of memory T cells^{2, 3, 4, 5, 6, 7}. The existence of immunological memory has been recognized for over 2,000 years, but our understanding of this phenomenon is limited, primarily because memory lymphocytes cannot be unequivocally identified as they lack specific, permanent markers. Here we have developed a transgenic mouse model system whereby memory T cells and their precursors can be irreversibly marked with a reporter gene and thus can be unambiguously identified. Adoptive transfer of marked CD8⁺ T cells specific for lymphocytic choriomeningitis virus protected naive recipients following viral challenge, demonstrating that we have marked memory T cells. We also show that cytotoxic effector lymphocytes that develop into memory T cells can be identified in the primary response.