Stimulation of human lymphocytes by a vaccine strain of Francisella tularensis

Abstract

An immune response to Francisella tularensis was demonstrated in man by the lymphocyte stimulation test. Peripheral blood lymphocytes were obtained from 26 individuals vaccinated with a viable tularemia vaccine, from 29 unvaccinated individuals, and from two patients who had recently undergone tularemia. The lymphocytes were incubated in the presence of various dilutions of heat-killed bacteria of the vaccine strain. The bacteria induced a deoxyribonucleic acid synthesis in the lymphocytes from 18 of the vaccinated individuals and from the two patients which was higher than that in the lymphocytes from any of the unvaccinated individuals. The deoxyribonucleic acid synthesis was maximal after about 6 days of incubation irrespective of concentration of bacteria. Lymphocytes from vaccinated and unvaccinated individuals were stimulated by two unrelated agents, tuberculin purified protein derivative and pokeweed mitogen. Lymphocytes from the vaccinated individuals did not show a higher response to these agents than did those of the unvaccinated. This suggests that the lymphocyte response to the Francisella bacteria was not due to a nonspecific activation. The vaccine-induced lymphocyte stimulation did not correlate with serum antibodies agglutinating F. tularensis antigen.

Stimulation of Subpopulations of Human Lymphocytes by a Vaccine Strain of Francisella tularensis

“…Lymphocyte stimulating agents. Heat-killed bacteria of F. tularensis LVS were prepared as previously described (28). Membranes of the bacteria were prepared following a modification used on Neisseria gonorrhoeae (34) which had originally been worked out for Escherichia coli (35).…”

“…Because this response becomes overt only in cultures of lymphocytes from sensitized subjects (20), it indicates the presence in the donor of an enlarged population of specifically committed lymphocytes. Recently, lymphocytes from tularemia-vaccinated individuals have been found to respond to antigen of the vaccine bacteria in vitro, whereas lymphocytes from nonvaccinated individuals responded poorly or did not respond at all (28). The purpose of the present study was to define the cell populations which are involved in the response.…”

Francisella tularensisvaccines

“…Although it is established that immunization of humans with LVS will protect against tularaemia, and the immune responses stimulated have been studied, the mechanisms essential for protection are unclear. Antibody responses can be used to monitor whether vaccination is successful, but do not correlate with specific lymphocyte responses in vaccinated humans (Tarnvik & Lofgren, 1975). Immune serum is not protective against highly virulent strains of F. tularensis, but can confer protection against low-virulence strains.…”

Immunogenicity and toxicity of lipopolysaccharide from Francisella tularensis LVS

“…Blood samples were obtained from six healthy adults previously vaccinated with F. tularensis LVS, and from four healthy adults denying knowledge of tularaemia or tularaemia vaccination. Lymphocytes were prepared from heparinized blood as previously described [29,30]. As antigen, LPS from F. tularensis was used at a concentration of 1.0 and 100 /~g ml -~.…”

“…Peripheral blood mononuclear adherent cells were prepared from heparinized blood of four human voluenteers as previously described [29,30]. The prepared cells (3 x 10 6 ml -~) were allowed to adhere to plastic culture dishes for 1-24 h in RPMI-1640 with 10% (v/v) inactivated normal human serum (obtained from healthy voluenteers) at 37°C.…”