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International Immunology, Vol. 3, No. 6, pp. 587-597,June 1991
© 1991 Japanese Society for Immunology
Establishment of resistance to Leishmania major infection in susceptible BALB/c mice requires parasite-specific CD8+ T cells
World Health Organization Immunology Research and Training Centre, Institute of Biochemistry, University of Lausanne 1066 Epalinges, Switzerland
1 Unité d'Immunophysiologie Cellulaire, Institut Pasteur 75724 Paris Cedex 15, France
Correspondence to: Correspondence to: J. A. Louis, W.H.O. - Immunology Research and Training Centre, Institute of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
Although CD4+ T cells are generally accepted to be responsible for the determination of resistance to infection in experimental murine cutaneous leishmanlasis, a contribution of CD8+ lymphocytes to immunity can be demonstrated under certain well-defined conditions. Normally highly susceptible BALB/c mice can be rendered resistant to infection with Leishmania major promastigotes by a single injection of monoclonal anti-CD4 antibodies at the beginning of infection. Mice treated in such a way can heal their primary cutaneous lesions and acquire immunity to subsequent challenge infection. Both the resolution of the primary infection and the induced state of immunityto reinfection in these mice is shown to be dependent upon the anti-leishmanial effector functions of CD8+ T cells. Furthermore, in contrast to control infected BALB/c mice, which are unable to mount a delayed-type hypersensitivity (DTH) response to viable parasites, mice cured as a result of treatment with anti-CD4 antibodies in vivo exhibit a strong DTH response, which can be significantly reduced by injection of either anti-CD4 or anti-CD8 monoclonal antibodies prior to antigenic challenge with viable promastigotes. Moreover, increased numbers of specific CD8+ T cells, able to transferLeishmania-specific DTH responses, were found in lymphold organs of BALB/c mice rendered resistant to infection by immunointervention with anti-CD4 monoclonal antibodies at the beginning of infection. Neutralization in vivo of interleukin 4 during the course of infection in BALB/c mice also enables these otherwise susceptible mice to resolve their cutaneous lesions and to decrease the parasite burden in infected tissues. CD8+ T cells are required for both of these beneficial effects. Taken together, these results indicate that in the immune BALB/c mouse, as in the normally resistant CBA mouse, CD8+ lymphocytes are involved in the elimination of L. major and in the establishment and maintenance of immunity against infection with this parasite.
Keywords: T cells, Leishmania major parasites
Received 21 January 1991, accepted 19 March 1991.
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