Inside these squares, single T cells taken from HIV-infected patients interact with infected cells. This technology, developed by MIT chemical engineers, offers the first way to study how effectively individual T cells respond to HIV-infected cells. Image: Navin Varadarajan |
One of the obstacles
to developing an effective AIDS vaccine is the difficulty in measuring how well
a potential vaccine primes the body to defend itself against HIV.
Ideally, scientists
would like their vaccines to provoke T cells, a critical component of the
immune response, to recognize and kill HIV-infected cells. Unfortunately, there
is no fast and easy way to monitor whether T cells are actually doing that.
Instead, researchers measure the amount of a protein called interferon gamma
that T cells secrete when they encounter an infected cell. Studies have shown,
however, that this “surrogate” measurement doesn’t necessarily predict a T
cell’s ability to kill HIV-infected cells.
In an advance that
could overcome that obstacle, a team of researchers at the Massachusetts
Institute of Technology (MIT) has developed a new technology that can measure
multiple aspects of individual T cells’ responses to HIV-infected cells,
including their ability to kill them. The technology could make it easier to
monitor and design vaccines against HIV, says J. Christopher Love, the Latham
Family Career Development Associate Professor of Chemical Engineering and
leader of the research team.
The technology, described in a paper published in the Journal of
Clinical Investigation, involves two steps. First, the researchers place
single T cells taken from HIV-infected patients into tiny wells on a plate, where
they are exposed to HIV-infected cells. The researchers can detect whether the
T cells kill the infected cells with probes that glow when the dying cells’
nuclei become compromised.
Next, the researchers
measure interferon gamma production with a microengraving technique they
developed in 2008. Secretions from each cell are imprinted on a glass
slide, which can then be tested for the presence of specific proteins. Because
each cell has its own “address” on the slide, the secretions can be traced back
to individual cells, and their interferon gamma production can be correlated
directly to their cell-killing ability.
The same technology
could be adapted to measure cells’ output of any other immune system protein.
In this study, the
researchers found that while the percentage of T cells that secrete interferon
gamma is similar to the percentage of those that kill infected cells, the
populations are not identical. In future studies, the researchers hope to find
markers that do correlate with cell-killing ability, making it easier to
evaluate a potential vaccine’s effectiveness.
“Now that we have a
tool to look directly at a variety of different functional activities, you can
go in and start to evaluate other markers that may be better predictors of
killing. Those then become what you would want to monitor in vaccine trials,”
says Love, who is also a member of the Ragon Institute of MGH, MIT and Harvard
and the David H. Koch Institute for Integrative Cancer Research at MIT.
“The appeal of this
technology is that it can help us understand more about what’s going on in
single cells,” says Alan Landay, professor of immunology and microbiology at Rush Medical
College. “It helps us
rethink what we understand about immunology and immune function.”
More research will be
needed to develop the technology to the point where it can be used routinely in
vaccine trials for large-scale studies of patient samples.
Filed Under: Drug Discovery
