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PROTEINS that fire up the immune system without the help of some key immune
cells could lead to vaccines that help people with AIDS fight off HIV.

Cells that are infected with viruses raise the alarm by displaying chopped-up
bits of protein from the pathogen on their surfaces. Cells of the immune system
called CD4 lymphocytes then tip off cytotoxic T-cells (CTLs), which kill any
cells with the same pathogen proteins on their surfaces.

This immune response is weak in patients with reduced numbers of CD4 cells,
including AIDS patients. But now scientists have discovered how to kick-start
the immune system without the help of these cellular middlemen.

The discovery follows work two years ago by Richard Young and his colleagues
at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts.
They triggered an immune response by injecting mice with heat-shock proteins
(HSPs), which are churned out by bacteria in stressful environments such as a
feverish human body.

The immune system attacked cells displaying HSPs on their surfaces, even
though there was no infection. 鈥淲e were very surprised,鈥� says Young. 鈥淲e thought
you needed intracellular infection.鈥�

The mice also mounted strong immune responses against any protein attached to
the HSPs. So viral proteins fused with HSPs might work as protein vaccines
against viruses.

To test this, Young鈥檚 team injected mice with HSP fused to a protein alien to
mice, called ovalbumin. As expected, CTLs from these mice killed mouse cells
engineered to produce ovalbumin in a dish.

The surprising result came when the team tried the same experiment in mice
without the CD4 cells that normally trigger CTLs. 鈥淭hese mice are like AIDS
patients in that they are enormously susceptible to infection,鈥� says Young. It
turned out that CTLs from these mice were just as effective at killing ovalbumin
cells as those of the normal mice.

The loss of CD4 cells in people with AIDS makes it hard for them to combat
HIV. Fusing an HIV protein to HSP might be a way around the problem, something
that Young is now testing in macaques infected with the monkey version of HIV.
鈥淚t鈥檚 not a magic bullet, but it might some day help keep the viral load down,鈥�
says Young.