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International Immunology, Vol. 6, No. 10, pp. 1535-1543,October 1994
© 1994 Japanese Society for Immunology

Intravenous injection of irradiated Leishmania major into susceptible BALB/c mice: immunization or protective tolerance

Toni Aebischer, Lynn Morris and Emanuela Handman

The Walter and Eliza Hall Institute of Medical Research PO Royal Melbourne Hospital, Victoria 3050, Australia

Correspondence to: Correspondence to. E. Handman

It is well established that BALB/c mice can be protected from fatal infection with Leishmania major by prophylactic intravenous (i.v.) immunization with irradiated parasites. Protection is critically dependent on the route of injection with i.v. injection being protective and subcutaneous injection not protective. We used this BALB/c-L major model system to investigate this phenomenon. We analyzed quantitatively the parasite-specific, CD4+ T cell mediated immune responses by limiting dilution. Subcutaneous vaccination resulted in priming of CD4+ precursor T cells, whereas i.v. vaccination was ineffectual. Moreover, i.v. injection prevented the increase in the number of specific precursor cells induced by infection of normal mice during the first weeks post-challenge with virulent parasites. We show here that this was not due to the elimination of the virulent challenge parasites as a result of immunity nor to inefficient antigen presentation of the irradiated organisms after i.v. injection, The data presented here suggest that i.v. injection results in tolerizatlon rather than immunization. Tolertzation as a mechanism of host protection is consistent with earlier observations that transient immunosuppresslon results in cure of L. major infection in BALB/c mice. Transfer of antigen presenting cells (APC) isolated from spleens of mice injected previously with irradiated parasites mimicked to some extent the effect of i.v. immunization with irradiated parasites. The possible involvement of these APC in decreasing the parasite-specific T cell response is discussed.

Keywords: intravenous immunization, limiting dilution analysis, lymphokines, T cell subsets

Received 22 April 1994, accepted 23 June 1994.


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