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P. M. Stuart, X.-T. Yin; Increased Corneal Allograft Rejection by Female Mice Is Associated With Significant Expansion of IL-17 Expressing Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1974.
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Corneal transplantation is one of the most common types of transplantation performed in this country with over 45,000 annually. It is also a form of transplantation that is uniquely successful with over 70% 5-year acceptance rate. However, 30% of recipients will reject their allografts and we are investigating some of the mechanisms involved in corneal allograft rejection.
We engrafted both male and female BALB/c mice with C57BL/6 corneas. We also performed similar studies on hormone treated female and male mice. Cultured cells from these mice were tested for cytokine expression by bioplex analysis.
Female mice display significantly greater rejection rates (60%) than do male mice (30%). Castrated male mice receiving estrogen treatment rejected with the same pattern as unmanipulated female mice. Likewise, ovarectomized female mice treated with testosterone rejected allogeneic corneal grafts in a fashion indistinguishable from unmanipulated male mice. Cultured spleen cells and lymph node cells from these mice revealed increased expression of several cytokines in female mice. However, intracellular staining of these cells only displayed significant increases IL-17 expressing cells (20% for female mice vs. 7% for male mice). Surprisingly, these cells did not express T cell markers for either CD4 or for CD8 but instead expressed surface markers consistent with neutrophils.
Female mice reject corneal allografts at almost twice the frequency as do male mice. This difference is directly due to levels of sex hormones in these mice. The mechanism that we favor for this response likely involves the preferential expansion of IL-17 expressing cells in female mice.
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