02420nas a2200289 4500000000100000008004100001260001300042653001200055653002400067653002100091653002300112653001700135653001800152653001200170653002600182653000900208653002500217653000900242653002100251100001600272700001700288245009600305300001200401490000700413520169600420022001402116 1990 d c1990 Feb10aAnimals10aAntigens, Bacterial10aImmune Tolerance10aImmunity, Cellular10aImmunization10aInterleukin-210aleprosy10aLymphocyte Activation10aMale10aMycobacterium leprae10aRats10aRats, Inbred Lew1 aWinters M A1 aHumphres R C00aInduction of antigen-specific immunity and tolerance to Mycobacterium leprae in Lewis rats. a495-5010 v583 a
Intradermal (i.d.) immunization of Lewis rats with autoclaved Mycobacterium leprae resulted in antigen-specific proliferation responses and interleukin-2 release from spleen and lymph node cells that were detectable as early as 21 days, persisted for at least 9 months, and were dependent on the dose of antigen administered. Immunized animals were also completely resistant to a footpad challenge with viable M. leprae. In contrast, intravenous (i.v.) administration of at least 10(8) irradiated M. leprae isolates induced a state of nonresponsiveness characterized by the absence of proliferation and interleukin-2 release by antigen-stimulated lymphoid cell cultures; however, in vitro responses to mitogenic stimulation and in vivo responses to keyhole limpet hemocyanin and Listeria monocytogenes were normal. Animals that received an i.v. injection of M. leprae remained nonresponsive to M. leprae antigens even after a subsequent i.d. immunization. This state of nonresponsiveness persisted for at least 6 months after induction. Results of footpad challenge experiments showed that the ability of animals rendered nonresponsive by an i.v. injection of M. leprae to control the growth of viable M. leprae in the footpad was not different from that of untreated rats. In addition, animals receiving an initial i.v. injection and a subsequent i.d. immunization with M. leprae were not protected from a viable challenge, as were rats that received only i.d. immunization. These results suggest that i.v. administration of a large dose of M. leprae to rats induces a state of nonresponsiveness to M. leprae antigens that may be similar to that seen in lepromatous leprosy patients.
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