Failure to expand influenza and tetanus toxoid memory T cells in vitro correlates with disease course in SIV infected rhesus macaques

Marked decreases in influenza (flu) and tetanus toxoid (T.T.) antigen speci fic CD8(+) and CD4(+) T cell memory responses were noted shortly after SIV infection in monkeys that go on to develop clinical disease within 18 month s (normal progressor, NP) following SIV infection but not in monkeys that r emain asymptomatic >3 years post SIV infection (long-term nonprogressor, LT NP). While PBMCs from NP and LTNP monkeys demonstrate both low and high avi dity flu and T.T. specific CD8(+) and CD4(+)T cell immune responses prior t o SIV infection, the PBMCs from NP but not LTNP fail to generate high avidi ty T cell responses post SIV infection. This failure to generate high avidi ty T cell responses in vitro correlated with increased apoptotic cell death in PBMC cultures from NP animals. Since high avidity antigen specific CTLs have been shown to be most efficient in eliminating viral infections, the present finding has important implications for the evaluation of the level of immune reconstitution following various modalities of therapy in HIV-1 i nfected patients. (C) 2001 Academic Press.