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A Yin-Yang Effect between Sex Chromosome Complement and Sex Hormones on the Immune Response

Departments of Neurology (K.M.P., D.L.S., S.K., R.R.V.) and Physiological Science (A.P.A.), University of California, Los Angeles, Los Angeles, California 90095; and Division of Developmental Genetics (P.S.B.), Medical Research Council, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom

Address all correspondence and requests for reprints to: Rhonda Voskuhl, Department of Neurology, University of California, Los Angeles, Los Angeles, California 90095. E-mail: rvoskuhl{at}ucla.edu.

Sex chromosome complement, by determining whether an ovary or testis develops, exerts indirect hormone-mediated effects on the development of sex-specific traits. However, this does not preclude more direct effects that are independent of gonadal hormones. To look for gonadal hormone-independent effects in sexually dimorphic immune responses, we used mice in which the testis determinant Sry has been moved from the Y chromosome to an autosome, thus allowing the production of mice that differ in sex chromosome complement while having the same gonadal type. This model permits comparison of XX and XY mice with ovaries or testes. These mice were immunized with an autoantigen, and draining lymph node cells were assessed for autoantigen-specific proliferative responses and cytokine production. Surprisingly, we found that the male complement of sex chromosomes (XY) was relatively stimulatory, whereas male sex hormones were inhibitory, for this immune response. This is the first experimental evidence of a compensatory yin-yang effect of sex chromosome complement and sex hormones on a biologic process.

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