TreatmentUpdate 55 - Vol. 7, No. 1; January 1995
Sean Hosein

Cytokines are chemicals (such as the interferons and interleukins) that are made by the immune system. The immune system releases certain cytokines to help recruit cells and manage the fight against infections. Once the infection is cured other cytokines are released which help to 'turn off' the response against the infection.

* TWO TYPES OF RESPONSES

There are two types of responses the immune system can make when it senses an infection. One response is called CMI (cell-mediated immunity, also known as a type 1 response). Very simply, CMI involves T cells that fight invading microbes and destroy infected cells. To boost CMI the immune system makes cytokines such as:

- interferon-gamma

- interleukin-2

- interleukin-12

As a general rule, CMI is needed to fight infections caused by viruses and other microbes that can infect and 'hide' inside cells.

The other type of response is called humoral immunity or type 2. Here the immune system relies on antibodies made by B-cells. To strengthen this response the immune system releases cytokines such as:

- interleukin-4 (IL-4)

- IL-6

- IL-10

Interestingly, these cytokines cause cells to make less of the cytokines needed for CMI. As well, interferon-gamma can cause cells to decrease production of the cytokines needed for humoral immunity.

* HIV

As a result of new discoveries on the cutting edge of immunology, researchers have began to form a more sophisticated model of HIV infection. When the immune system first detects HIV it can make a response based largely on antibodies or it may try and contain the infection using T cells. Those people whose immune systems make the antibodies become "HIV-positive". Despite making large amounts of antibodies, most patients eventually develop AIDS. Several research teams have found people who have been exposed to HIV, yet did not make antibodies. Instead, their immune systems appeared to contain and manage the infection using T cells. Some researchers suggest that, over time, those HIV-antibody positive patients make less of the chemicals that can boost CMI while making more of the chemicals that help humoral immunity. This shift in cytokine balance favouring humoral immunity may also be why patients with HIV/AIDS become allergic to drugs. As CMI weakens, life- threatening infections appear. Eventually, humoral immunity also weakens.

* EARLY WARNING

Based on results of experiments with cells and HIV, it appears that HIV-infected immune systems become less able to detect invading microbes. Moreover, even when T cells are given a 'description' of the microbe(s) they are supposed to attack, their attempts are weak and the infection is not always contained. In much of the basic research on HIV it is clear that CD8+ cells are important in helping fight off many of the infections seen in AIDS. These cells also play a role in managing the immune system and should not be thought of as simple 'suppressor' cells. In the next report we present findings on cytokine therapy.

ACKNOWLEDGEMENTS:

1. Thanks to B. Goldberg for helpful discussions, access to research papers and researchers.

REFERENCES:

1. Mossmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone: definition according to profile of lymphokine activities and secreted proteins. Journal of Immunology 1986;136(7):2348-2357.

2. Mossmann TR. Cytokine patterns during progression to AIDS. Science 1994;265:193-194.

3. Clerici M and Shearer G. The Th1-Th2 hypothesis of HIV infection: new insights. Immunology Today 1994;15(12):575-581.

4. Rowland-Jones S, Sutton S, Ariyoshi K, et al. HIV-specific cytotoxic T cells in HIV-exposed but uninfected Gambian women. Nature Medicine 1995;1(1):59-64.

5. Meyaard B, Otto SA, Keet IPM, et al. Changes in cytokine patterns of CD4+ T cell clones in Human Immunodeficiency Virus infection. Blood 1994;84(12):4262-4268.

6. Maggi E, Giudizi MG, Biagiotti R, et al. Th2-like CD8t cells showing B cell helper function and reduced cytolytic activity in Human Immunodeficiency Virus type-1 infection. Journal of Experimental Medicine 1994;180:489-495.

7. Paganlli R, Scala E, Ansotegui LJ, et al. CD8+ T lymphocytes provide helper activity for IgE synthesis in Human Immunodeficiency Virus-infected patients with hyper-IgE. Journal of Experimental Medicine 1995;181:423-428.

8. Seder RA and Le Gros GG. The functional role of CD8+ T helper type 2 cells. Journal of Experimental Medicine 1995;181:5-7.

9. Quill H, Bhandoola A, Trinchieri G, et al. Induction of ILr12 responsiveness is impaired in anergic T lymphocytes. Journal of Experimental Medicine 1994;179:1065-1070.

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Copyright © 1995 - 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