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Gender Differences in the Expression of Proteins in Autoreactive T-cells Specific to Central Nervous System Myelin Proteolipid Protein 139-151

Background: Autoimmune diseases are more prevalent in women than in men, and such a disparity also exists in animal models. In our studies with the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein 139-151 (PLP) for multiple sclerosis, gender differences are well documented, in that only female, but not male, SJL mice show chronic relapsingremitting paralysis. Since EAE is typically mediated by CD4 T cells, we tested a hypothesis that the generation and expansion of antigen-specific CD4 T cells might be different between genders.

Methods and findings: First, by creating a newer and more sensitive version of major histocompatibility complex class II tetramers called dextramers, we noted no differences in the generation of PLP-specific T cells in the peripheral repertoires of male and female SJL mice. Second, comparable numbers of PLP-specific T cells were found to be infiltrated into the brains of both genders as verified by flow cytometric analysis. Third, evaluation of molecules that positively or negatively regulate the expansion of effector T cells revealed that expression of cytotoxic T-lymphocyte associated protein 4 was tended to be more in the T cells that infiltrate into the brains of male than female mice. Finally, we analyzed the proteomic profiles in PLP 139-151- specific T cells to identify additional novel molecules that may potentially contribute to the gender-disparity in the development of central nervous system autoimmunity. In conjunction with tandem mass spectrometric analysis and ingenuity pathway analysis, we have identified a panel of proteins found to be expressed gender dependently, suggesting that they can be regulated by sex steroids.

Conclusions: Our data revealed expression of proteins that can potentially play a role in the development of diseases of multiple organs such as the central nervous system and cardiovascular system including cancers.


Chandirasegaran Massilamany, Renu Nandakumar, Nandakumar Madayiputhiya, Sanjit Pandey, Chittibabu Guda and Jay Reddy

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