AIDS TREATMENT NEWS Issue #189, December 17, 1993
John S. James
Two of the researchers on this study, Mario Clerici, M.D., and Gene M. Shearer, Ph.D., proposed a theory earlier this year of a "TH1-to-TH2 switch" -- a change in immune function which occurs in HIV infection, and may cause the disease to progress faster.(2) According to this theory -- which is accepted by many but not all researchers -- in early HIV infection, the body first defends itself effectively against the virus by one kind of response (called the TH1 response; 'TH' stands for T-helper); this response consists mainly of cellular immunity, i.e. certain cells which destroy infected cells. But then, while the patient is still asymptomatic, the immune system switches to a TH2 response, which mainly produces antibodies, which appear to be less effective than cellular immunity in controlling HIV infection. Each kind of response tends to suppress the other; so when the switch to a TH2 response occurs, the protective TH1 response is largely lost. IL-12 may reverse this switch and restore cellular immunity against HIV and other pathogens.
Two teams, Genetics Institute, Inc., Cambridge, Massachusetts, working with the Wistar Institute, Philadelphia, Pennsylvania, and Hoffmann-La Roche, Inc., Nutley, New Jersey, each independently discovered IL-12. Genetics Institute and Wistar initially named their discovery Natural Killer-cell Stimulatory Factor (NKSF). Roche named its discovery Cytotoxic Lymphocyte Maturation Factor (CLMF). Genetics Institute and Roche have agreed to cross-license each other so that each company may proceed independently in the further development of IL-12.
A December 10 news release from the National Cancer Institute explained the new IL-12 study. It is the best description for non-scientists, so we reproduce it in full:
"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 Hoffmann-La Roche, Inc., Nutley, New Jersey. 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, Maryland, along with researchers at Lackland Air Force Base, San Antonio, Texas, and Genetics Institute Inc., Cambridge, Massachusetts, performed the current study, which appears in the December 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 proliferation, interleukin-2 (IL-2) production, and interferon-gamma (IFN-gamma) production. (These cells did not 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., and others, unpublished results). Preliminary (phase I) studies of IL-12 in HIV-infected people are being planned by the manufacturer, Genetics Institute, Inc., and should begin in the first half of 1994."
References
1. Clerici M, Lucey DR, Berzofsky JA, and others. Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro. SCIENCE. December 10, 1993; volume 262, pages 1720-1724.
2. Clerici M and Shearer GM. A TH1-->TH2 switch is a critical step in the etiology of HIV infection. IMMUNOLOGY TODAY. March 1993; volume 14, number 3, pages 107-111.
931217
ATN18902
Copyright © 1993 - AIDS Treatment News. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. Subscription lists are kept confidential. AIDS Treatment News, Subscription and Editorial Office: 1233 Locust St., 5th floor Philadelphia, PA 19107 800/TREAT-1-2 toll-free email: aidsnews@critpath.org http://www.aidsnews.org
Subscription Information: Call 800/TREAT-1-2: Businesses, Institutions, Professionals: $270/year. Includes early delivery of an extra copy by email. Nonprofit organizations: $135/year. Includes early delivery of an extra copy by email. Individuals: $120/year, or $70 for six months. Special discount for persons with financial difficulties: $54/year, or $30 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1993. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1980, 1993. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .