Newly Recognized Connection Between Immune System and Sperm Opens Window to Some Male Infertility and Cancer Vaccine Failures Interview with:
Kenneth S. K. Tung, M.D.
Professor of Pathology and Microbiology
Director of UVA Research Histology Core
Beirne B. Carter Center for Immunology Research
University of Virginia What is the background for this study?

Response: The immune system needs to see tissue antigens to avoid responding to them in order to prevent autoimmune disease development. The current dogma, stated in all Immunology and Reproductive Biology textbooks, considers the sperm antigens in the testis to be exempted from this process. They are considered totally hidden behind a tissue barrier, and are invisible to the immune system.

Because sperm antigens are treated as foreign molecules, they should stimulate strong immune response when employed in cancer vaccines against antigens common to sperm and cancers. It is also believed that sperm molecules are protected by local factors that inhibit inflammation, whereas systemic mechanisms such as regulatory T cells would not exist.

The paradigm has restrained ongoing research on systemic tolerance to sperm, and the need to understanding systemic regulation in infertility research What are the main findings?

  1. Showed that only some sperm antigens are hidden, other sperm antigens are exposed to immune system.
  2. Identified a new physiological pathway that exports the exposed sperm antigens from the testis.
    3. Identified regulatory T cells as a systemic mechanism that prevents autoimmunity to the exposed sperm antigens; their depletion can lead to spontaneous testis autoimmune disease and male infertility.
    4. In contrast, the hidden antigens are the target of autoimmune response in vasectomy, a procedure that exposes the hidden sperm antigens.

Response: Our results represent a paradigm shift in the understanding in the immunology of sperm antigens.

The new information are relevant to our understanding of immune infertility and the selection of more effective cancer vaccine antigens that are shared between cancers and sperm (so-called cancer-testis antigens). What should readers take away from your report?

  1. A shift in paradigm has occurred on testis immunology: sperm antigens sequestration is selective and not complete.
  2. Research on systemic mechanisms, particularly regulatory T cells, is germane in sperm antigen research.
  3. Research on local mechanisms should include those that can: a) be anti-inflammatory and b) promote systemic tolerance.
  4. The exposed and hidden sperm antigens are dominantly involved in spontaneous infertility and vasectomy, respectively.
  5. The hidden sperm antigens should be more effective when employed as anti-cancer vaccinogens.
  6. The existence of systemic protection by regulatory T cells in normal men may interfere with anti-cancer immunity when they express the exposed sperm antigens in their cancer cells. Thank you for your contribution to the community.


Kenneth S.K. Tung, Jessica Harakal, Hui Qiao, Claudia Rival, Jonathan C.H. Li, Alberta G.A. Paul, Karen Wheeler, Patcharin Pramoonjago, Constance M. Grafer, Wei Sun, Robert D. Sampson, Elissa W.P. Wong, Prabhakara P. Reddi, Umesh S. Deshmukh, Daniel M. Hardy, Huanghui Tang, C. Yan Cheng, Erwin Goldberg. Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance. Journal of Clinical Investigation, 2017; 127 (3): 1046 DOI: 10.1172/JCI89927

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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