I have used the transfer of primed lymphocytes into syngeneic irradiated recipients to investigate whether the persistence of antigen is required in the long-term maintenance of cytolytic T cell memory to influenza virus. Animals were immunized with influenza virus (A/WSN) and used 17 wk later as either donors for T cells or as lethally irradiated recipients. Naive age-matched mice served as controls. At intervals of 4, 8, 16, and 25 wk after T cell transfer, experimental and control groups were immunized with a heterologous virus (A/JAP) and splenocytes tested for lytic activity to influenza virus 3 and 6 d after immunization. Lytic activity 3 d after infection (a property exclusive to a memory cytotoxic T cell response) (Effros, R. B., J. Bennink, and P. C. Doherty. 1978. Cell. Immunol. 36:345.; and Hill, A. B., R. V. Blanden, C. R. Parrish, and A. Müllbacher. 1992. Immunol. Cell Biol. 70:259), was only observed by primed and naive irradiated recipients reconstituted with memory T cells. No day 3 responses were observed when naive T cells were transferred into irradiated primed or unprimed recipients. These observations demonstrate that cytolytic T cell memory to influenza virus is long lived in the absence of antigen.

Müllbacher, A. (1994). The long-term maintenance of cytotoxic T cell memory does not require persistence of antigen. The Journal of Experimental Medicine, 179(1), 317–321.