Stimulation of the CD2 receptor pathway induces apoptosis in human T lymphotropic virus type I-infected cell lines.
We demonstrate that CD2 receptor engagement, but not CD3 crosslinking, induces apoptosis in lymphocytes transformed by human T-cell lymphotrophic virus type I (HTLV-I). Mitogenic pairs of anti-CD2 monoclonal antibodies inhibited [3H]thymidine incorporation from 25 to 62% in CD2+ HTLV-I-infected lymphocytes. This inhibition was associated with a 20-40% reduction in cell number and viability over a 3-day period, morphologic evidence of apoptosis, and irreversible DNA fragmentation. While cyclosporin A abrogated CD2-mediated proliferation in peripheral blood mononuclear cells, it had no effect on CD2-induced apoptosis in the HTLV-I-infected cell lines. Since HTLV-I is mitogenic to resting lymphocytes through CD2 activation pathways, these results suggest that HTLV-I-infected lymphocytes are primed for apoptosis following additional CD2 stimulation. This CD2-mediated apoptosis might be a factor in immune regulation of HTLV-I-associated diseases or might offer a novel adjunctive approach to treatment.
Guyot
D J
DJ
Center for Retrovirus and Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, USA.
Trask
O J
OJ
Andrews
J M
JM
Newbound
G C
GC
Lairmore
M D
MD
D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D018801:CD2 Antigens / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival; D016572:Cyclosporine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000821:virology
D015703:Antigens, CD; D018801:CD2 Antigens; D016572:Cyclosporine; D004247:DNA