Polyclonal Rabbit Antithymocyte Globulin Exhibits Consistent Immunosuppressive Capabilities Beyond Cell Depletion

Abstract

This novel, systematic in vitro analysis of 14 different manufactured lots of thymoglobulin demonstrates the overall consistency of this product and provides further insights into nondepletive mechanisms by which thymoglobulin may generate durable immunoregulation and allograft survival.

Transient Low-Dose Methotrexate Induces Tolerance to Murine Anti-Thymocyte Globulin and Together They Promote Long-Term Allograft Survival

“…In fact, although T regulatory cells associated with transplantation tolerance (24,30,31,43) are induced by Thymoglobulin and mATG (23,25,26,32,33) and are responsible for mATGmediated prolonged graft survival (16), we did not see increases in T regulatory cells with the mATG and methotrexate combination over that of mATG alone. In addition, there was no evidence of enhanced depletion of T cells, and only a modest extension of mATG effects was observed as a result of blockade of anti-drug Ab responses by methotrexate.…”

“…In particular, as T regulatory cells have been associated with longterm graft survival in transplantation (23,24,30,31), are induced by Thymoglobulin and mATG (22,25,26,32,33), and have previously been demonstrated to be responsible for delayed graft rejection following mATG (16), CD3 + Foxp3 + cells, which bear a phenotype consistent with regulatory T cells, were evaluated. To assess histologic changes in long-surviving grafts, cardiac grafts were collected from the mATG and methotrexate combinationtreated group and the untreated syngeneic group at least 100 d after transplantation.…”

Immune Monitoring of Kidney Recipients: Biomarkers to Appreciate Immunosuppression -Associated Complications

“…Analysis of CD45RA, CD45RO, CD27 and CD31 marker expression on T cells from both adult and pediatric renal transplant recipients suggests that Treg comes from both RTE and peripheral expansion in adult patients, while they are mainly derived from thymus in children (Gurkan et al, 2010). Furthermore, ATG may also alter T cell migration (LaCorcia et al, 2009) and naive T cells have to home to secondary lymphoid organs in order to maintain a stable population size. A subset of stromal cells present in the secondary lymphoid organs, called fibroblastic reticular cells supports T cell survival (Link et al, 2007).…”

CD4 T Lymphopenia, Thymic Function, Homeostatic Proliferation and Late Complications Associated with Kidney Transplantation

“…In-depth analysis of Treg phenotype after ATG treatment using CD45RA, CD45RO, CD27 and CD31 markers suggests that Treg come from both thymus and peripheral expansion in adult renal transplant recipients, while they are mainly derived from thymus in pediatric patients [75]. Furthermore, ATG may also alter T cell migration [79] and naive T cells have to home to secondary lymphoid organs in order to maintain a stable population size [53]. A subset of stromal cells present in the secondary lymphoid organs, called fibroblastic reticular cells supports T cell survival via CCL19 [80].…”