Selected articles May 2015
Aire-deficient mice can be used as a model for autoimmune infertility
Autoimmunity, Not a Developmental Defect, is the Cause for Subfertility of Autoimmune Regulator (Aire) Deficient Mice
E. Kekäläinen, N. Pöntynen, S. Meri, T. P. Arstila and H. Jarva
In this study carried out by Finnish researchers it is confirmed that Aire-deficient mice suffer from adaptive immune system - dependent infertility. These findings indicate that Aire-knockouts can be used also as a model of male infertility of autoimmune origin.
The autoimmune regulator (AIRE) protein is a transcriptional regulator, whose most described function is to promote ectopic expression of tissue-specific antigens in the thymic medulla for presentation to developing T cells. This expression is the basis for deleting autoreactive developing thymocytes and when AIRE is missing, the autoreactive T cells are able to complete their maturation and eventually cause autoimmunity. In addition, AIRE is involved in developmental processes.
Patients that lack AIRE suffer from a disease called autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) that is characterized by multiple autoimmune attacks against mainly endocrine organs. In addition, infertility is a common problem in these patients.
Aire-deficient mice are used as a model for APECED and in the present study the researchers wanted to resolve whether or not the reduced fertility observed in Aire-deficient mice is dependent on the adaptive immune system, and therefore a manifestation of autoimmunity in these mice. In order to address this question lymphopenic mice without Aire, AireRag1 mice, were created
Eliisa Kekäläinen was a PhD student when this study was carried out and was involved in all of the stages of the project.
– I planned and conducted the breeding experiments, did the cell transfers, and also wrote the manuscript, she says.
Eliisa Kekäläinen says that the whole project was a spinoff of a previous project with the same AireRag1 mice that has been also published in the Scandinavian Journal of Immunology.
– We created the AireRag1 model for this other project but accidentally noted that they bred normally even though the parental Aire-deficient strain did not.
The group show that whereas Aire-deficient males had a significantly reduced breeding capacity, the AireRag1-males, who lack functional T and B cells, regained full fertility. This fertility was again lost when AireRag1-males were adoptively transferred with lymphocytes from Aire-deficient donors. Thus the Aire-deficient male mice have a lymphocyte-dependent infertility, making them a good model for human autoimmune infertility.
New insights into clinical regulatory T cell sorting
Immunological Profiling of Haemodialysis Patients and Young Healthy Individuals with Implications for Clinical Regulatory T Cell Sorting
M. Bergström, A.-L. Joly, P. Seiron, S. Isringhausen, E. Modig, B. Fellström, J. Andersson and D. Berglund
In the study, by a Swedish research group, flow cytometry was used to assess peripheral blood lymphocyte profiles of young healthy individuals and patients undergoing haemodialysis treatment. The study show an overall similar immunological profile of both cohorts in spite of great differences in both age and health.
Patients that have undergone organ transplants require lifelong treatment with immunosuppressive drugs to prevent acute transplant rejection. This leads to an elevated risk for, amongst other, infections and cancer and therefore novel strategies for these patients are being investigated. One approach involves adoptive transfer of regulatory T cells (Tregs) that suppress the immune system via multiple mechanisms. To use these cells in therapy it is important to optimize and standardize the identification of Tregs and to elucidate possible differences between potential Treg donors.
In this study, the immunological profiles of healthy blood donors and patients undergoing hemodialysis treatment was analyzed. In particular, identification of Tregs using flow cytometry was performed, and the Treg-marker FOXP3 mRNA expression was studied.
– We have been able to statistically show and visually depict the differences in FOXP3 purity after flow cytometric sorting depending on which cell surface antigens and cell populations that are selected for, says Marcus Bergström, PhD student in transplantation immunology and first author of the study.
During this work, Marcus Bergström enjoyed the collaboration between various research groups and people with different areas of expertise.
– This can sometimes be challenging but ultimately very rewarding.
Marcus Bergström also appreciated the privilege of taking part in and supporting the development of cell based therapies.
– It’s a marathon, but every addition takes us a few steps closer to the to goal. We hope that our findings will come to use in the isolation of regulatory T cells for clinical therapy, for example in hematopoietic stem cell transplantation or in the prevention of kidney transplant rejection.