B7-2 (CD86) is essential for the development of IL-4-producing T cells.
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 alpha beta 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-gamma, 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-gamma, 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.
Ranger
A M
AM
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.
Das
M P
MP
Kuchroo
V K
VK
Glimcher
L H
LH
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000378:metabolism / Q000494:pharmacology; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology
D019138:Antibodies, Blocking; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D015847:Interleukin-4