Interleukin-12 an integral cytokine in the immune response

被引:84
作者
Stern, AS
Magram, J
Presky, DH
机构
关键词
interleukin-12; T cells; NK cells; Th1; cells; interferon-gamma; adaptive immunity;
D O I
10.1016/0024-3205(95)02247-3
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Interleukin 12 (IL-12) is a heterodimeric cytokine that is produced primarily by antigen-presenting cells and plays a primary role in the induction of cell-mediated immunity. This function is promoted by the IL-12 induced production of interferon-gamma (IFN-gamma) from both resting and activated NK and T cells, by the proliferative activity of IL-12 on activated NK and T cells, by enhancing the cytotoxic activity of NK cells, and by supporting cytotoxic T lymphocyte generation. IL-12 and IL-12 induced IFN-gamma promote the development of naive T cells into Th1 cells and the proliferation and IFN-gamma secretion by differentiated Th1 cells in response to antigen. IL-12 has been found to exhibit many of these activities in vivo, as well as in vitro, and thus IL-12 plays an important role in both innate resistance and antigen-specific adaptive immunity to intracellular bacterial, fungal, and protozoan pathogens. Due to its effects on T cells, recombinant IL-12 has been shown to have therapeutic activity in a variety of mouse tumor and infectious disease models and is being evaluated in clinical trials in human cancer patients. IL-12 also appears to play a role in the genesis of some forms of immunopathology, including endotoxin-induced shock and some autoimmune diseases associated with aberrant Th1 activity. Therefore, IL-12 antagonists may also have therapeutic potential in the treatment of auto immune disorders.
引用
收藏
页码:639 / 654
页数:16
相关论文
共 137 条
[1]   THE ADJUVANT EFFECT OF INTERLEUKIN-12 IN A VACCINE AGAINST LEISHMANIA-MAJOR [J].
AFONSO, LCC ;
SCHARTON, TM ;
VIEIRA, LQ ;
WYSOCKA, M ;
TRINCHIERI, G ;
SCOTT, P .
SCIENCE, 1994, 263 (5144) :235-237
[2]  
ANDREWS JVR, 1993, J IMMUNOTHER, V14, P1
[3]  
ARAGANE Y, 1994, J IMMUNOL, V153, P5366
[4]   COOPERATION OF NATURAL-KILLER-CELL STIMULATORY FACTOR INTERLEUKIN-12 WITH OTHER STIMULI IN THE INDUCTION OF CYTOKINES AND CYTOTOXIC CELL-ASSOCIATED MOLECULES IN HUMAN T-CELLS AND NK-CELLS [J].
ASTEAMEZAGA, M ;
DANDREA, A ;
KUBIN, M ;
TRINCHIERI, G .
CELLULAR IMMUNOLOGY, 1994, 156 (02) :480-492
[5]   INTERLEUKIN-12 (IL-12) INDUCES TYROSINE PHOSPHORYLATION OF JAK2 AND TYK2 - DIFFERENTIAL USE OF JANUS FAMILY TYROSINE KINASES BY IL-2 AND IL-12 [J].
BACON, CM ;
MCVICAR, DW ;
ORTALDO, JR ;
REES, RC ;
O'SHEA, JJ ;
JOHNSTON, JA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (01) :399-404
[6]  
BERTAGNOLLI MM, 1992, J IMMUNOL, V149, P3778
[7]  
BLOOM ET, 1994, J IMMUNOL, V152, P4242
[8]  
BONNEMA JD, 1994, J IMMUNOL, V152, P2098
[9]   MULTIPLE EFFECTS ON PERIPHERAL HEMATOLOGY FOLLOWING ADMINISTRATION OF RECOMBINANT HUMAN INTERLEUKIN-12 TO NONHUMAN-PRIMATES [J].
BREE, AG ;
SCHLERMAN, FJ ;
KAVIANI, MD ;
HASTINGS, RC ;
HITZ, SL ;
GOLDMAN, SJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 204 (03) :1150-1157
[10]   ROLE OF INTERFERON-GAMMA IN MEDIATING THE ANTITUMOR EFFICACY OF INTERLEUKIN-12 [J].
BRUNDA, MJ ;
LUISTRO, L ;
HENDRZAK, JA ;
FOUNTOULAKIS, M ;
GAROTTA, G ;
GATELY, MK .
JOURNAL OF IMMUNOTHERAPY, 1995, 17 (02) :71-77