B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy
| Autor: | Mercy Prabhu Das, Vijay K. Kuchroo, Julia A. Brown, Raymond A. Sobel, Nasrin Nabavi, Ann M. Ranger, Laurie H. Glimcher, Howard L. Weiner, Scott S. Zamvil |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Proteolipids T cell Encephalomyelitis medicine.medical_treatment Molecular Sequence Data Mice Transgenic Biology Immunotherapy Adoptive General Biochemistry Genetics and Molecular Biology Interferon-gamma Mice Th2 Cells Antigen Antigens CD medicine Animals Amino Acid Sequence Cells Cultured Autoimmune disease Membrane Glycoproteins Biochemistry Genetics and Molecular Biology(all) Vaccination Antibodies Monoclonal CD28 Cell Differentiation Myelin Basic Protein Immunotherapy Th1 Cells medicine.disease medicine.anatomical_structure Immunology B7-1 Antigen biology.protein Female Cytokine secretion B7-2 Antigen Interleukin-4 Lymph Nodes Antibody |
| Zdroj: | Cell. 80:707-718 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/0092-8674(95)90349-6 |
| Popis: | CD4 T helper precursor cells mature along two alternative pathways, Th1 and Th2. Here we show that these pathways are differentially activated by two costimulatory molecules, B7-1 and B7-2. Using anti-B7 antibodies, this developmental step was manipulated both in vitro and in vivo in experimental allergic encephalomyelitis (EAE). Anti-B7-1 reduced the incidence of disease while anti-B7-2 increased disease severity. Neither antibody affected overall T cell induction but rather altered cytokine profile. Administration of antiB7-1 at immunization resulted in predominant generation of Th2 clones whose transfer both prevented induction of EAE and abrogated established disease. Since cotreatment with anti-IL-4 antibody prevented disease amelioration, costimulatory molecules may directly affect initial cytokine secretion. Thus, interaction of B7-1 and B7-2 with shared counterreceptors CD28 and CTLA-4 results in very different outcomes in clinical disease by influencing commitment of precursors to a Th1 or Th2 lineage. |
| Databáze: | OpenAIRE |
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