The role of IL-12 in the maintenance of an established Th1 immune response in experimental leishmaniasis.
IL-12 initiates the development of cell-mediated immunity by promoting the differentiation of naive T cells into the Th1 phenotype, and is essential in the development of a Th1 immune response to the intracellular protozoan parasite, Leishmania major. The present study investigated whether IL-12 is also required for the maintenance and effector function of an established Th1 immune response in L. major-infected mice. While neutralization of IL-12 compromised the ability of a leishmanial antigen-reactive Th1 cell clone to produce IFN-gamma in vitro, lymph node cells taken from 2-week L. major-infected mice were able to secrete IFN-gamma in an IL-12-independent manner. However, when a short-term T cell line was established in vitro from lymph node cells, the production of IFN-gamma again became IL-12 dependent. These results suggest that other factors may compensate for IL-12 in vivo in promoting IFN-gamma production during L. major infection. To directly assess if IL-12 was required in vivo for resistance to L. major, we studied the effect of IL-12 neutralization on both a primary and secondary L. major infection in C3H mice. L. major infection in C3H mice is characterized by the development of a small lesion that heals by 8 weeks, and these animals are resistant to reinfection. As previously reported, administration of anti-IL-12 monoclonal antibody (mAb) during a primary infection led to severe disease. However, mice that had healed from a primary infection with L. major and were treated with anti-IL-12 mAb were as resistant as control animals. These findings suggest that once Th1 cells have developed, their effector function in vivo is independent of IL-12, and that this independence is not due to an intrinsic property of the T cell, but to the microenvironment created by the infection.
Department of Pathobiology, University of Pennsylvania, Philadelphia 19104, USA.
C S
CS
Constantinescu
B D
BD
Hondowicz
M M
MM
Elloso
M
M
Wysocka
G
G
Trinchieri
P
P
Scott
D000818:Animals; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D007896:Leishmaniasis / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D018417:Th1 Cells / Q000276:immunology*
D018664:Interleukin-12; D007371:Interferon-gamma