One Mechanism for Why Men, Women Differ in Immune Response

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One Mechanism for Why Men, Women Differ in Immune Response

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Decreasing testosterone boosts immunity because testosterone helps control

T-lymphocytes, the attack cells of the immune system, according to Mayo

Clinic-led research in laboratory animals.

Newswise ‹ Decreasing testosterone boosts immunity because testosterone

helps control T-lymphocytes, the attack cells of the immune system,

according to Mayo Clinic-led research in laboratory animals. The findings

appear in the Nov. 15 edition of the Journal of Immunology

(http://www.jimmunol.org/future/173.10.shtml ).

Collaborators include scientists from Roswell Park Cancer Institute,

Buffalo, N.Y.; the Tumor Immunity and Tolerance Section of the Laboratory of

Molecular Immunoregulation, National Cancer Institute; and

Medical Institute/Memorial Sloan-Kettering Cancer Center.

³What we are showing is that testosterone seems to impede immunity,² says

Eugene Kwon, M.D., the Mayo Clinic urologist and immunology researcher who

led the research team. ³However, when testosterone is withdrawn, you get an

increased host immune response indicated by the rising numbers of immune

cells that are available to participate.²

T-lymphocytes are cells that are vital to controlling the body¹s immune

response. ³T cells,² as they are usually called by scientists, are white

blood cells that can fight against tumor cells and infection. Alternatively,

T cells can help other immune cells known as ³B cells² make antibodies to

defend the body against certain bacterial and fungal infections, and

possibly against cancer. The research findings may have broad potential

applications to public health. For example, knowing that testosterone levels

affect T-cell response may help:

* explain why women are more prone than men to develop ³autoimmune disease.²

* speed the development of drugs that bolster the immune system to treat

such immune-deficiency diseases as AIDS.

* improve vaccines.

* decrease the time needed to reconstitute the immune system after bone

marrow transplantation.

* protect cancer patients who are receiving immunotherapy treatments or who

are vulnerable to infection as a result of chemotherapy.

Significance of the Research

Researchers and physicians have known for years that there is a difference

in immunity between men and women -- but they have not known why. The

researchers discovered one possible mechanism driving the difference: The

presence of testosterone slows or weakens the response of T-lymphocytes.

Delving further to discover the mechanism behind this response, the research

team found that without testosterone, the T-lymphocytes ³turn-on² more

quickly.

It also is possible that other sex hormones play a similar role because

testosterone is just one of the hormones known as androgens.

³Females are typically more predisposed to the phenomenon of autoimmunity,²

says Dr. Kwon. ³And of course, what¹s interesting about this is that females

don¹t have significant levels of testosterone. Men, on the other hand, may

have relatively blunted immune responses and have high levels of

testosterone. So these results of our experiment are really very promising

for unraveling this gender difference in the immune system.² He emphasizes

that further research is needed to validate these findings before they can

be used in human patients in the clinic.

Background Biology

Dr. Kwon frequently cares for patients with prostate cancer. The current

experiment grew out of his experience in the clinic. One of the more common

forms of treatment for prostate cancer suppresses the patient¹s testosterone

levels to increase the patient¹s immune attack against cancer. To test the

role of testosterone on the immune system in the laboratory, the researchers

removed testosterone from male mice.

³They suddenly started growing large numbers of new immune cells,² Dr. Kwon

says. ³We also demonstrated that if you take a male mouse and treat it with

chemotherapy you can prompt the mouse to recover its immune system much more

quickly simply by removing androgen.²

When testosterone is removed, the immune cells come back strong and

aggressive, ready to attack. Says Dr. Kwon, ³They become twitchy, very

reactive, and in this state they can, in fact, mediate a strong immune

response -- which, as physicians, is just what we want.²

Collaborators and Support

In addition to Dr. Kwon, Mayo Clinic research team members include Anja C.

Roden, M.D., D. Tri, Mercader, Ph.D., M. Kuntz, Haidong

Dong, M.D., Ph.D., J. McKean, Ph.D., Esteban Celis, M.D., and Bradley

C. Leibovich, M.D. Collaborators from other institutions are: T.

Moser, Roswell Park Cancer Institute; Arthur A. Hurwitz, principal

investigator, Tumor Immunity and Tolerance Section, Laboratory of Molecular

Immunoregulation, National Cancer Institute; and P. , chairman,

Immunology Program, H. Koch Chair in Immunologic Studies, Attending

Immunologist, Department of Medicine, Investigator, Medical

Institute, Memorial Sloan-Kettering Cancer Center. The work was supported by

a National Institutes of Health National Cancer Institute grant; a U.S.

Department of Defense grant; and the Mayo Foundation.