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A controversial theory of AIDS that could force vaccine researchers
back to square one has gained new support. Å®ÉúСÊÓƵs in Canada say their
studies on animals add weight to the idea that HIV does not attack the immune
system directly, as most biologists believe. Rather, they believe the virus
provokes the immune system into attacking itself. If they are right, then
vaccines that aim to stimulate the immune system might not work; they could
even speed up the course of the disease.

Since the late 1980s, a few dissident researchers in Britain, the US
and Canada have argued that AIDS is an autoimmune disease. Their theory
is based partly on the finding that HIV’s envelope protein, gp120, seems
to mimic the shape of certain crucial proteins in the body’s own immune
system. These proteins, called Class II MHC antigens, are found on the surface
of cells, and without them, the T cells of the immune system cannot ‘recognise’
foreign material or respond to it. But because gp120 looks like certain
MHC antigens, antibodies against the viral protein may also attack the MHC
antigens, says the theory. The more the immune system reacts to HIV, the
more it attacks itself.

The Canadian team, led by Geoffrey Hoffmann, is at the University of
British Columbia in Vancouver. They say that foreign lymphocytes entering
the body from another individual may trigger a second immune response that
in turn fights the first response. Such foreign cells – for example in blood
or seminal fluid – carry MHC receptors against the host, and these provoke
a response from the recipient’s immune system. According to the team, the
result is that the first and the second immune response each sees the other
as ‘the enemy’, even though each was provoked by something else. The resulting
clash between the two immune responses upsets the delicate balance between
mutually dependent sets of helper T cells and suppressor T cells.

Now the Canadian team has studied the immune systems of mice. They examined
mice from a strain that suffers autoimmune disease and mice from another
strain which has been exposed to other mouse cells. The second strain is
known as allo-immune because it has developed an immune response to the
foreign cells.

Even though none of the mice had ever been exposed to HIV, both strains
produced antibodies to the virus (Science, vol 253, p 1138). This finding
lends support to the idea that the virus has evolved to mimic MHC antigens,
say the researchers. The autoimmune mice had antibodies that specifically
recognised gp120. The allo-immune mice had antibodies to gp120 and, even
more surprisingly, antibodies to a core protein of HIV, p24. In addition,
the researchers found the mice had ‘anti-anti MHC’ antibodies – in other
words, antibodies that look like MHC antigens because they are in fact the
mirror image of antibodies to MHC antigens. Together, these findings are
‘the strongest evidence so far for the theory’, says Hoffmann. He believes
that future vaccines and therapies would need to ‘suppress the part of the
immune response that is going haywire’, rather than stimulate it.

Other scientists are cautious but intrigued. Bruce Forrest, AIDS vaccines
clinical trials coordinator for Britain’s Medical Research Council, said:
‘This is a particularly interesting and important observation that needs
more study.’