CATIE HIV/AIDS THEORY - Repairing the immune system

HIV/AIDS THEORY - Repairing the immune system

TreatmentUpdate43: Vol. 4, No. 3, July, 1993
Sean Hosein

Analysis of the work done by NCI scientists suggests that maintaining CMI (the Th1 response) can "prevent HIV infection and/or progression to AIDS." This has implications for the care and treatment of people with HIV infection:

* Infections (other than HIV) which can cause the immune response to switch from one based on CMI to that based on antibody responses could act as cofactors, speeding up the decline of the immune system. Examples of these types of diseases might include tuberculosis (TB) and syphilis. Thus diagnosis, treatment and prevention of other infections becomes increasingly important.

* Instead of giving HIV-infected subjects large doses of the viral proteins gp160 and gp120 in vaccination experiments, perhaps very small doses should be used instead. Low doses might be enough to stimulate T-cell functions but not strong enough to trigger the production of antibodies by B-cells.

* Screening people with HIV infection into those with a good CMI response from others with a good humoral response could be a first step in a new direction for therapy. Those subjects with a good humoral response could be given antibodies that attacked IL-4, IL-10 and other chemicals of the immune system. This may return their immune response to a more effective phase. Researchers at military biomedical centres in the USA have performed experiments on T-cells taken from people with a good humoral response. They exposed those T-cells to antibodies that attacked IL-4 which then reversed the decline in CD4+ cell functioning.

* Other ways to boost cell-mediated immunity could include giving people infusions of low dose interferon-gamma and IL-2.

* Dr. Jonas Salk and researchers at the NCI have proposed that very low doses of the live TB vaccine (BCG) could also help but this has to be tested for safety in experiments before being given to larger numbers of people with HIV infection.

* Based on this research there may be a limited role for the immune boosters acemannan (Carrisyn(R)), DNCB and the hormone DHEA in maintaining T-cell functions. We should point out that researchers do not know the best dose and schedule for using DHEA in people with HIV infection. None of these three drugs is a cure for AIDS. As research in this field is only just beginning to occur it will be some time before researchers learn which combination of these or other agents will be most useful.

REFERENCES: 1. Clerici M, Shearer GM. A TH1->TH2 switch is a critical step in the etiology of HIV infection. Immunology Today 1993;14(3):107-111.

2. Goldberg B . Cellular and antibody immune responses in AIDS (personal communication*). *Data on file at CATIE.

3. Clerici M, Hakim FT, Venzon DJ, et al. Changes in interleukin- 2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. Journal of Clinical Investigation 1993;91:759-765.

4. Romagnani S. Human Th1 and Th2 subsets:regulation of differentiation and role in protection and immunopathology. International Archives of Allergy and Immunology 1992;98:279-285.

5. Fitzgerald TJ. The Th1/Th2-like switch in syphilitic infection:is it detrimental? Infection and Immunity 1992;60(9):3475-3479.

6. Meyaard L, Schuitemaker H and Miedema F. T-cell dysfunction in HIV infection: anergy due to defective antigen-presenting cell function? Immunology Today 1993:161

7. Knight SC, Macatonia SE and Patterson S. Infection of dendritic cells with HIV-1: virus load regulates stimulation and suppression of T-cell activity. Research in Virology 1993;144:7580.

8. Salk J, Bretscher PA, Salk PL, et al. A strategy for prophylactic vaccination against HIV. Science 1993;260:1270-1272.

9. Manetti R, Parronchi P, Giudizi M, et al. Natural killer cell stimulatory factor (Interleukin-12 [IL-12]) induces T helper type 1(Th1) specific responses and inhibits the development of IL-4 producing Th cells. Journal of Experimental Medicine 1993;177:1199-1204.

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Copyright © 1993 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca

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