Selected Articles June 2016
On immunosuppressive treatment during pregnancy
Changes in the Immune System of Female Wistar Rats After Exposure to Immunosuppressive Treatment During Pregnancy
J. Kabat-Koperska, A. Kolasa-Wołosiuk, B. Wojciuk, I. Wojciechowska-Koszko, P. Roszkowska, B. Krasnodębska-Szponder, E. Paczkowska, K. Safranow, E. Gołembiewska, B. Machaliński and K. Ciechanowski
In this study, researchers from Poland show that there are qualitative, quantitative and morphological changes of the immune system in pharmacologically immunosuppressed female Wistar rats.
Female graft recipients are advised to become pregnant at least 1–2 years after successful kidney transplantation, when graft function is good and stable. In this period, a reduction in doses of immunosuppressive drugs is possible with acceptable low danger of acute rejection. Some immunosuppressive drugs are considered to be relatively safe during pregnancy while others are contraindicated due to their toxicity. However, experience regarding the use of many immunosuppressive drugs in human pregnancy is limited.
In this experimental study, the researchers assessed the impact of ‘safe’ and ‘contraindicated’ drugs in combinations (the ones most frequently used in therapy of human kidney recipients) on changes in the immune system of female Wistar rats after exposure during pregnancy.
Joanna Kabat-Koperska is the first author of this study and a senior assistant in the group.
– I designed this study, collected and interpreted the data and wrote the manuscript, she explains.
This publication is part of J.Kabat-Koperska´s scientific achievement that she prepared to apply for a habilitation degree in Poland.
Most previous studies focused on immunotoxicity were carried out on male rats, but here the group focus on female, pregnant rats, and find that thymus structure, spleen composition and splenocytes IL17 production were mostly affected in a drug regimen-dependent manner.
In summary, the researchers observed some important alterations in composition of splenic lymphocytes and their function on the basis of changed production of cytokines in female rats exposed to different combinations of immunosuppressive drugs during pregnancy. Altered sensitivity to immunotoxins or immune-modulating drugs can be expected in humans as well as the immune system of human changes during pregnancy, for example reflected by the frequent improvement of symptoms of rheumatoid arthritis.
Immature phenotype of regulatory T cells in neonates
Healthy Preterm Newborns Show an Increased Frequency of CD4+CD25highCD127lowFOXP3+ Regulatory T Cells with a Naive Phenotype and High Expression of Gut-Homing Receptors
C. Rennó, M. I. V. Nadaf, C. A. Zago, M. Carneiro-Sampaio andP. Palmeira
Here, Brazilian researchers have investigated the frequency of T regulatory cells (Tregs) in neonates and show differences in weight and gestational age among three groups of newborns (moderate and very preterm newborns, late preterm newborns and full-term newborns), which demonstrate the importance of a detailed division into groups.
Tolerance to self-antigens is a highly regulated process, and to maintain it, the immune system must be able to distinguish autoreactive lymphocytes and their development. Tregs are particularly important for the maintenance of immune homoeostasis, and failures in their development and function are the primary causes of a fatal autoimmune and inflammatory disease as evidenced in both humans and mice, which results from a mutation in the forkhead box P3 gene (FOXP3), the master transcription factor expressed in Treg.
The establishment of normal baseline values of Treg in healthy human newborns and how they are numerically and proportionately affected by prematurity provides the basis for further investigation into the function of these cells. Several authors have described reference values for leucocyte subpopulations in full-term neonates but few have analysed the same parameters in preterm newborns.
Camila Rennó was a Master's degree student in Dr Patricia Palmeira´s lab and designed the overall study with her supervisor and collected samples at the Obstetric Center.
– I performed the experiments, analyzed and interpreted the data, and wrote the manuscript with Dr Patricia Palmeira, she explains.
The differences in weight and gestational age among the three groups of newborns shown in this publication can also be seen in the phenotyping results, such as the number of circulating leucocytes, which probably reflects the dynamic developmental phases, in which a difference of only a few days during pregnancy already shows a different degree of maturity.
Although higher frequencies of Treg cells are present in term and preterm newborns compared with adults and these are inversely correlated with gestational age, an immature phenotype with a higher expression of CD45RA and α4β7/α4β1 and a lower expression of CTLA-4 is found, particularly in the very preterm group.
– This could imply lower functional activity of these cells in neonates, particularly in the very preterm group, Camila Rennó concludes.