Fernandez and Mitsuda reactivity in guinea pigs sensitized with heat-killed Mycobacterium leprae: persistence and specificity of skin reactivity to soluble and particulate antigens.

Guinea pigs were sensitized with 500 micrograms dry weight of heat-killed Mycobacterium leprae, M. tuberculosis H37Rv, M. vaccae, or M. nonchromogenicum suspended in saline. Significant Fernandez (peak swelling at 48 hr) and Mitsuda (peaking at 21 days) reactions were observed when all four groups of animals were skin tested with 10 micrograms of the homologous whole-cell antigen (WCA) preparations one month after sensitization. Some of the guinea pigs were given a booster injection of the homologous suspension three months later and were then retested with the four WCA preparations. The Fernandez (rather than the Mitsuda) reactivity was enhanced by the second immunization and was still substantial when tested eight months after boosting. The Mitsuda-type responses observed 12 months after the primary sensitization peaked earlier than in the first- and four-month tests, regardless of the vaccinating organism. The M. leprae-sensitized guinea pigs produced larger Fernandez skin reactions than those seen in the other three groups of sensitized animals, but there was substantial crossreactivity between M. leprae and M. tuberculosis antigens, as well as somewhat lesser responsiveness in the M. vaccae- or M. nonchromogenicum-sensitized animals skin tested with lepromin. The present study indicates that saline suspensions of heat-killed M. leprae induced a highly persistent state of lepromin hypersensitivity which was quantitatively superior to that observed in animals sensitized with the three other mycobacteria.