EXPANSION OF V-GAMMA-9V-DELTA-2 T-CELLS IS TRIGGERED BY FRANCISELLA TULARENSIS-DERIVED PHOSPHOANTIGENS IN TULAREMIA BUT NOT AFTER TULAREMIAVACCINATION

Tularemia is a disease caused by the facultative intracellular bacteri um Francisella tularensis. Here we demonstrate that during the first w eeks off infection, a significant increase in levels of V gamma 9V del ta 2 cells occurred in peripheral blood: in 13 patients analyzed 7 to 18 days after the onset of disease, these lymphocytes represented, on average, 30.5% of CD3(+) cells and nearly 100% of gamma delta(+) T cel ls, By contrast, after vaccination with the live vaccine strain (LVS) of F. tularensis, only a minor increase occurred, Eleven days after va ccination, gamma delta T cells represented an average of 6.7% and V ga mma 9V delta 2 cells represented an average of 5.3% of T cells, as in control subjects, Since derivatives of nonpeptidic pyrophosphorylated molecules, referred to as phosphoantigens, are powerful stimuli for V gamma 9V delta 2 cells, this observation prompted an investigation of phosphoantigens in F. tularensis strains, The F. tularensis phosphoant igens triggered in vitro a proliferative response of human V gamma 9V delta 2 peripheral blood leukocytes as well as a cytotoxic response an d tumor necrosis factor release from a V gamma 9V delta 2 T-cell clone , Quantitatively similar phosphoantigenic activity was detected in ace llular extracts from two clinical isolates (FSC171 and Schu) and from LVS, Taken together, the chemical nature of the stimulus from the clin ical isolates and the significant increase in levels of V gamma 9V del ta 2 cells in peripheral blood of tularemia patients indicate that pho sphoantigens produced by virulent strains of F. tularensis trigger in vivo expansion of gamma delta T cells in tularemia.