Table of Contents

Volume 3, Issue 1

  January/February/March 2012

View covers archive

REVIEW

Open Access Article

Immigration control in the vertebrate body with special reference to chimerism

Anthony J.S. Davies
Abstract | Full Text | PDF

The phenomenon of chimerism is reviewed against an understanding of adaptive immunity in vertebrates. It is shown that chimerism can be regarded as a ubiquitous condition and this suggests that monophylesis has played little part in evolution. It is suggested that the adaptive immune response has a special role in facilitating the development of chimerism and that the consensus view of adaptive immunity as a rejection mechanism should be revised.




RESEARCH PAPER

Open Access Article

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

Gurvinder Kaur, Neeraj Kumar, Ramya Nandakumar, Chowphi C. Rapthap, Gaurav Sharma, Shekhar Neolia, Heena Kumra, Prateek Mahalwar, Abhinav Garg, Sunil Kumar, Jasmeet Kaur, Mrinali Hakim, Lalit Kumar and Narinder K. Mehra
Abstract | PDF

Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.




BRIEF REPORT

Open Access Article

Fetal-maternal interface: A chronicle of allogeneic coexistence

Josep-Maria Pujal, Santiago Roura, Ana M. Muñoz-Marmol, Jose-Luis Mate and Antoni Bayes-Genis
Abstract | PDF

The existence of allogeneic cells within an individual has been demonstrated in multiple fields such as hematopoietic stem cell or solid organ transplantation, non-depleted blood transfusions and the most common form which is bidirectional maternal-fetal cell trafficking, whereby cells from the fetus pass through the placental barrier. In order to graphically illustrate this early natural phenomenon that initiates the journey of a child’s cells within the mother’s blood and other tissues, we used a new procedure in microscopy imaging generating Large Scale Panoramic Pictures (LSPP). This technique can also be extended to explore a broad diversity of experimental models.




ARTICLE ADDENDA

Open Access Article

Fetal microchimeric cells in blood and thyroid glands of women with an autoimmune thyroid disease

Trees Lepez, Mado Vandewoestyne and Dieter Deforce
Abstract | Full Text | PDF

Persistence of fetal microchimeric cells may result in the development of autoimmune thyroid diseases (AITD) such as Hashimoto thyroiditis (HT) or Graves disease (GD). In women, HT and GD show an increased incidence in the years following parturition. Although fetal cells have already been shown to be more common in the thyroid glands of patients with an AITD compared with controls, these cells haven’t been described in blood of these patients. Our study detected fetal cells in blood of all patients with an AITD. Moreover, fetal cells were immune cells potentially capable of initiating a graft vs. host reaction and suggest a potential role of these cells in the pathogenesis of AITD. Our study indicates the value and need for further research in this field.

Open Access Article

Tolerance induction after organ transplantation, “delayed tolerance,” via the mixed chimerism approach: Planting flowers in a battle field

Yohei Yamada, Gilles Benichou, A. Benedict Cosimi and Tatsuo Kawai
Abstract | Full Text | PDF

We have previously reported that peri-transplant conditioning leads to successful induction of renal allograft tolerance via the mixed chimerism approach in nonhuman primates (NHP) and humans. However, this strategy requires treatments beginning six days prior to transplantation, which limits its relevance only to living donor transplant recipients. To extend the clinical applicability of this approach, we developed a novel regimen “delayed tolerance,” with which the recipient initially undergoes organ transplantation with conventional immunosuppression, followed by conditioning and donor bone marrow transplantation (DBMT) at a later date. This approach might be likened to “planting flowers in a battle field.” That is, the recipient’s immunologic environment after organ transplantation is like a battlefield filled with hostile innate and adaptive immune-responses directed against donor antigeneic specificities. Implanting fragile donor hematopoietic progenitors into this environment and encouraging them to bloom in this vicious field requires special treatments.

 

In our NHP studies recently published in The American Journal of Transplantation, we showed that such “delayed tolerance,” in fact, can be induced in NHP through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T cell responses are provided. These modifications include adequate depletion of CD8 memory T cells and timing of donor bone marrow administration to minimize levels of pro-inflammatory cytokines. This article addendum will provide a short summary of the original paper with our additional insights and interpretations.