Details

Autor(en) / Beteiligte

• Constantinescu, Cris S.
• Hondowicz, Brian D.
• Merle Elloso, M.
• Wysocka, Maria
• Trinchieri, Giorgio
• Scott, Phillip

Titel

The role of IL‐12 in the maintenance of an established Th1 immune response in experimental leishmaniasis

Ist Teil von

• European journal of immunology, 1998-07, Vol.28 (7), p.2227-2233

Ort / Verlag

Weinheim: WILEY‐VCH Verlag GmbH

Erscheinungsjahr

1998

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 com promised the ability of a leishmanial antigen‐reactive Th1 cell clone to produce IFN‐γ in vitro, lymphnode cells taken from 2‐week L. major ‐infected mice were able to secrete IFN‐γ 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‐γ again became IL‐12 dependent. These results suggest that other factors may compensate for IL‐12 in vivo in promoting IFN‐γ 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.