There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
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 anti-B7-1 at immunization resulted in predominant generation of Th2 clones whose
transfer both prevented induction of EAE and abrogated established disease. Since
co-treatment 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.