快猫短视频

Science : Altered cells flip the immune system’s off switch

Immunologists know that it is sometimes possible to prevent an immune
response to a protein. But the new experiments, described last month at a
Keystone Symposium on immunology in Hilton Head, South Carolina, are the first
to turn off a response that has already started. This is important for
researchers working on autoimmune diseases, which develop without warning.
鈥淧eople don鈥檛 go to their doctor and say, `I think I鈥檓 going to develop an
autoimmune disease in 10 years鈥,鈥 says David Scott of the American Red Cross in
Rockville, Maryland.

The immune system鈥檚 T and B cells only attack proteins when they appear in a
certain way鈥攐n the surface of antigen-presenting cells, and when some
other biochemical warning signal is present (快猫短视频, Science, 30
March, p 14
). So the immune system can sometimes ignore proteins if, for
example, they are released by B cells.

Scott and his colleague Elias Zambidis bred mice carrying B cells that were
genetically engineered so that an antibody they secreted called immunoglobulin G
incorporated a protein from a virus that infects bacteria. When the researchers
injected these animals with the foreign protein, there was no immune response.
And when they took B cells from these animals and injected them into normal
mice, they also ignored the protein.

But the real surprise came when Scott and Zambidis injected the altered B
cells into mice that had already been 鈥減rimed鈥 to attack the viral protein. The
animals suddenly began to produce less antibodies to the protein. 鈥淭o our
knowledge, no one has done this before,鈥 says Scott.

This sharp drop in antibody production only occurred when the altered B cells
had first been exposed to a bacterial toxin that made them produce large amounts
of the immunoglobulin. Unstimulated B cells failed to switch off the immune
response to the protein. Scott does not know if the animals鈥 immune systems were
lulled into a state of 鈥渢olerance鈥, or whether the large doses of viral protein
simply exhausted the animals鈥 immune defences.

Daniel Mueller of the University of Minnesota, a specialist on immunological
tolerance, says the findings are 鈥減rovocative鈥, but warns that more work is
needed before the same approach can be applied to autoimmune disease. Scott鈥檚
next aim is to repeat his mouse experiments using B cells that have been
designed to secrete immunoglobulin incorporating the nerve sheath protein that
is attacked in multiple sclerosis.

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