Blood Component Could Help Immune Cells Fight AIDS
National Cancer Institute (NCI) scientists have succeeded in restoring normal immune responses to cultured cells from HIV-infected donors. The scientists used a natural blood substance, interleukin-12 (IL-12), which will be tested in asymptomatic HIV-positive individuals within the next several months. HIV is the virus responsible for AIDS.
T lymphocytes from many HIV-infected people do not show normal immune reactions when they are exposed to antigens such as influenza virus. By adding the immune regulator IL-12 to cultures of these cells, the NCI scientists and their colleagues were able to augment the cells' immune reactions.
"In the test tube, this is the most powerful immune response modulator we have seen," said Gene M. Shearer, Ph.D., of the National Cancer Institute's Experimental Immunology Branch.
IL-12 was identified in 1991 by scientists at the Wistar Institute, Philadelphia, and Hoffman-La Roche, Inc., Nutley, N.J. It is an interleukin -- one of a class of proteins produced by lymphocytes that transmit signals to regulate growth of immune cells.
Mario Clerici, M.D., Shearer, and their colleagues at NCI and the National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Md., along with researchers at Lackland Air Force Base, San Antonio, Tex., and Genetics Institute Inc., Cambridge, Mass., performed the current study, which appears in the Dec. 10 issue of Science.
The investigators tested white blood cells from HIV-negative and HIV-positive individuals by exposing cultures of the cells to several antigens, including influenza virus and synthetic versions of HIV envelope peptides. Cells from HIV-negative donors reacted to antigens with T cell react to the HIV envelope peptides, however, because of the donors' lack of previous exposure to HIV.)
Cells from HIV-positive individuals did not respond fully to any of the test antigens unless IL-12 was added. In the presence of IL-12, the cultures reacted normally to challenge with the antigens, showing T cell proliferation, IL-2 production, and IFN-gamma production. The immune responses of cells from HIV-negative donors were normal whether or not IL-12 was added.
Shearer and Clerici have previously shown that, in HIV-infected individuals, a switch from one pattern, type 1, of interleukin production to a different pattern, type 2, is associated with disease progression. The type 1 pattern principally enhances cellular immunity, while type 2 is linked with antibody production. Because Shearer and Clerici believe that cellular immunity is more effective than antibodies in combating HIV infection, they have been interested in finding ways to promote the type 1 pattern. The results of the current study suggest that IL-12 may have this effect.
NIAID scientists recently tested IL-12 in mice with a disease similar to AIDS and found that it had a positive effect on the animals' immune function (Ricardo Gazzinelli, Ph.D., et al., unpublished results). Preliminary (Phase I) studies of IL-12 in HIV-infected people are being planned by the manufac- turer, Genetics Institute, Inc., and should begin in the first half of 1994.
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