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Ben May Institute for Cancer Research, Committee on Immunology, Department of Pathology, University of Chicago, IL 60637
Anti-CD3 mAbs with low FcR affinity prolong graft survival in the
absence of the cytokine-mediated toxicity observed with conventional
anti-CD3 treatment. Previous studies have shown that FcR-nonbinding
anti-CD3 mAbs suppress immune responses, at least in part, by
delivering a partial signal resulting in Th1 unresponsiveness. In this
study, the biochemical and functional consequences of FcR-nonbinding
anti-CD3 treatment for various activated T cell populations were
examined. In contrast to Th1 cells, FcR-nonbinding anti-CD3-treated
Th2 cells secreted IL-4 and proliferated. Furthermore, Th2 cells
cultured with the mAb were not rendered unresponsive. Mixed "Th0"
populations responded to FcR-nonbinding anti-CD3 by producing IL-4,
and showed a selective decrease in IL-2 production following preculture
with the mAb. The stimulation of IL-4-producing cells did not reflect a
more complete TCR signal, since similar defects in 
, ZAP-70, and MAP
kinase phosphorylation were observed in Th1 and Th2 cells. Despite the
proximal signaling defects, FcR-nonbinding anti-CD3 induced nuclear
translocation of NF-ATc. Thus, Abs that deliver partial TCR signals may
promote development of a Th2 phenotype during the course of an immune
response via selective effects on different Th subsets.
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