Transient low-dose methotrexate induces tolerance to murine anti-thymocyte globulin and together they promote long-term allograft survival.

Rabbit anti-thymocyte globulin (Thymoglobulin) effectively treats transplant rejection but induces anti-rabbit Ab responses, which limits routine readministration. Aiming to tolerize anti-rabbit responses, we coadministered a brief methotrexate regimen with a murine version of Thymoglobulin (mATG) for effects on anti-mATG Abs and cardiac allotransplantation in mice. Although both single and three courses of methotrexate could significantly inhibit anti-drug Ab titers to repeated mATG treatment, surprisingly, the single course given at the first mATG administration was most effective (>99% reduction).

Murine antithymocyte globulin T-cell depletion is mediated predominantly by macrophages, but the Fas/FasL pathway selectively targets regulatory T cells.

Background: Thymoglobulin is a T-cell-depleting polyclonal rabbit anti-human thymocyte antibody used clinically for immunosuppression in solid organ and hematopoietic stem-cell transplantation. By using a surrogate rabbit anti-mouse thymocyte globulin (mATG), we previously demonstrated that murine regulatory and memory T cells are preferentially spared from mATG depletion in vivo. The current studies were designed to determine whether different effector mechanisms are involved in differential depletion of T-cell subsets by mATG.

In vivo characterization of rabbit anti-mouse thymocyte globulin: a surrogate for rabbit anti-human thymocyte globulin.

Background: Polyclonal rabbit anti-human thymocyte globulin (Thymoglobulin) is used clinically for immunosuppression in solid organ transplantation; however, it is difficult to fully characterize the effects of this agent in humans.

Methods: A surrogate rabbit anti-murine thymocyte globulin (mATG) was generated analogously to the commercial product Thymoglobulin and in vivo activities were evaluated, including pharmacokinetics, T-cell depletion, dose response and kinetics, depletion/sparing of T-cell subsets or other leukocyte populations, and depletion in different lymphoid organs.

Results: Within 1 day, T cells are depleted by mATG in the blood, spleen, lymph node, and bone marrow down to doses of 1 mg/kg.

Pharmacology of AMD3465: a small molecule antagonist of the chemokine receptor CXCR4.

CXCR4 is widely expressed in multiple cell types, and is involved in neonatal development, hematopoiesis, and lymphocyte trafficking and homing. Disruption of the CXCL12/CXCR4 interaction has been implicated in stem cell mobilization. Additionally CXCR4 is a co-receptor for HIV.