BMJ 2002;324:320 ( 2 February )
Scott Gottlieb New York
Scientists believe they may have identified a way to turn off the immune response when patients receive a transplanted organ or bone marrow by manipulating T cells, which are key players in initiating and conducting immune responses.
In previous studies researchers identified a special group of T cells, called suppressor T cells, which can shut down the normal function of other important immune system cells called monocytes and dendritic cells.
Normally, monocytes and dendritic cells help trigger immune responses. In the current study, a team of researchers, led by Dr Nicole Suciu-Foca of Columbia University in New York, has found how suppressor T cells work.
They observed that when monocytes and dendrite cells were exposed to suppressor T cells in the laboratory, levels of two inhibitory proteins, ILT3 and ILT4, increased on their surfaces. The upregulation of these inhibitory proteins rendered the monocytes and dendritic cells tolerant to foreign substances from donor tissue. The study has been published early on the web in Nature Immunology (www.nature.com/ni/main.html).
In the experiment, the researchers looked at blood samples from patients who had received heart transplants without rejecting them. They saw that the tolerant suppressor T cells in these blood samples had high levels of ILT3 and ILT4. These proteins, they found, were responsible for shutting down monocytes found in the heart donors and thus for preventing organ rejection. The researchers speculate that it might be possible to make transplant recipients tolerant of donor tissue simply by treating the tissue with a drug that increases levels of ILT3 and ILT4.
As ILT3 and ILT4 are believed to constitute one of the central mechanisms of tolerance, and specifically the inhibitory activity shown by regulatory T cells, the study’s authors said that the results have implications for other medical problems, including autoimmune diseases, allergies, and immune deficiency disorders.
By manipulating the expression of
ILT3 and ILT4 in these diseases, the researchers said that they hope that
one day they will be able to modulate immune responses beneficially. The
proteins may also have implications for diseases in which the problem is
not too much stimulation of the immune system, but too little.