B7–2 (CD86) is essential for the development of IL-4-producing T cells

• Published in: International immunology Vol. 8; no. 10; pp. 1549 - 1560
• Main Authors: Ranger, Ann M., Das, Mercy Prabhu, Kuchroo, Vijay K., Glimcher, Laurie H.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.1996; Oxford Publishing Limited (England)
• Subjects: Animals; Antibodies, Blocking - pharmacology; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, CD - pharmacology; B7-1 Antigen - metabolism; B7-1 Antigen - pharmacology; B7-2 Antigen; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Separation; co-stimulation; cytokine; differentiation; Immunoglobulin Fab Fragments - pharmacology; Interleukin-4 - biosynthesis; Interleukin-4 - pharmacology; Lymphocyte Activation - drug effects; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - pharmacology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Recombinant Proteins - pharmacology; Spleen - cytology; T cell; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; T-Lymphocytes, Helper-Inducer - cytology; Th1
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/8.10.1549

The CD28/CTLA-4 ligands, B7–1 (CD80) and B7–2 (CD86), provide a co-stimulatory signal necessary for optimal T cell activation. We have examined the effect of blocking B7–1 and B7–2 in an in vitro system using ovalbumin-specific T cells from αβ TCR-transgenic mice. This system allowed us to examine the interaction of B7 co-stimulators on physiologic antigen-presenting cells (APC) with antigen-specific T helper precursor (Thp) cells. We report that blocking Thp/B7–1 or B7–2 interactions in a primary response differentially affects the cytokine profile observed in a secondary stimulation, even in the absence of additional anti-B7 antibody. Engagement of B7–2 in the primary stimulation was found to be essential for production of the Th2 cytokine, IL-4, but not the Th1 cytokines, IL-2 and IFN-γ, in a secondary stimulation. Conversely, inclusion of the anti-B7–1 mAb in cultures using highly purified naive T cells increased levels of IL-4 and significantly depressed levels of IFN-γ, upon re-stimulation. The effect of the anti-B7–2 mAb in reducing IL-4 production could be overcome by the addition of recombinant IL-4 in the primary stimulation. The effects of the anti-B7–2 mAb appear to be due to blocking and not cross-linking, as F(ab) fragments mimicked the intact antibody. Taken together, our data demonstrate that the interaction between Thp and B7–2 favors the development of Th2 cells.