In the absence of IL-12, CD4+ T cell responses to intracellular pathogens fail to default to a Th2 pattern and are host protective in an IL-10-/- setting

被引:208
作者
Jankovic, D [1 ]
Kullberg, MC [1 ]
Hieny, S [1 ]
Caspar, P [1 ]
Collazo, CM [1 ]
Sher, A [1 ]
机构
[1] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1016/S1074-7613(02)00278-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-12-deficient mice exposed to nonlethal infections with intracellular pathogens or repeatedly immunized with a pathogen extract developed lowered but nevertheless substantial numbers of IFN-gamma(+) CD4(+) T cells compared to those observed in wild-type animals. Moreover, the CD4(+) responses in these knockout animals failed to default to a Th2 pattern. The protective efficacy of the Th1 cells developing in an IL-12-deficient setting was found to be limited by IL-10 since mice doubly deficient in IL-10 and IL-12 survived, while animals deficient in IL-12 alone succumbed to pathogen challenge. In contrast to IL-12 knockout mice, MyD88-deficient animals exposed to a Th1 microbial stimulus developed a pure Th2 response, arguing that this signaling element plays a more critical function than IL-12 in determining pathogen-induced CD4 polarization.
引用
收藏
页码:429 / 439
页数:11
相关论文
共 83 条
[1]   STRATEGIES OF ANTICYTOKINE MONOCLONAL-ANTIBODY DEVELOPMENT - IMMUNOASSAY OF IL-10 AND IL-5 IN CLINICAL-SAMPLES [J].
ABRAMS, JS ;
RONCAROLO, MG ;
YSSEL, H ;
ANDERSSON, U ;
GLEICH, GJ ;
SILVER, JE .
IMMUNOLOGICAL REVIEWS, 1992, 127 :5-24
[2]   Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].
Adachi, O ;
Kawai, T ;
Takeda, K ;
Matsumoto, M ;
Tsutsui, H ;
Sakagami, M ;
Nakanishi, K ;
Akira, S .
IMMUNITY, 1998, 9 (01) :143-150
[3]   Toll-like receptors and innate immunity [J].
Akira, S .
ADVANCES IN IMMUNOLOGY, VOL 78, 2001, 78 :1-56
[4]   Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency [J].
Altare, F ;
Durandy, A ;
Lammas, D ;
Emile, JF ;
Lamhamedi, S ;
Le Deist, F ;
Drysdale, P ;
Jouanguy, E ;
Döffinger, R ;
Bernaudin, F ;
Jeppsson, O ;
Gollob, JA ;
Meinl, E ;
Segal, AW ;
Fischer, A ;
Kumararatne, D ;
Casanova, JL .
SCIENCE, 1998, 280 (5368) :1432-1435
[5]   A natural model of Leishmania major infection reveals a prolonged "silent" phase of parasite amplification in the skin before the onset of lesion formation and immunity [J].
Belkaid, Y ;
Mendez, S ;
Lira, R ;
Kadambi, N ;
Milon, G ;
Sacks, D .
JOURNAL OF IMMUNOLOGY, 2000, 165 (02) :969-977
[6]   DELAYED HYPERSENSITIVITY-TYPE GRANULOMA FORMATION AND DERMAL REACTION INDUCED AND ELICITED BY A SOLUBLE FACTOR ISOLATED FROM SCHISTOSOMA MANSONI EGGS [J].
BOROS, DL ;
WARREN, KS .
JOURNAL OF EXPERIMENTAL MEDICINE, 1970, 132 (03) :488-+
[7]   IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes [J].
Brombacher, F ;
Dorfmüller, A ;
Magram, J ;
Dai, WJ ;
Köhler, G ;
Wunderlin, A ;
Palmer-Lehmann, K ;
Gately, MK ;
Alber, G .
INTERNATIONAL IMMUNOLOGY, 1999, 11 (03) :325-332
[8]   Identification of STAT4-dependent and independent mechanisms of resistance to Toxoplasma gondii [J].
Cai, GF ;
Radzanowski, T ;
Villegas, EN ;
Kastelein, R ;
Hunter, CA .
JOURNAL OF IMMUNOLOGY, 2000, 165 (05) :2619-2627
[9]   Interleukin-18 (IL-18) enhances innate IL-12-mediated resistance to Toxoplasma gondii [J].
Cai, GF ;
Kastelein, R ;
Hunter, CA .
INFECTION AND IMMUNITY, 2000, 68 (12) :6932-6938
[10]  
CHATELAIN R, 1992, J IMMUNOL, V148, P1182