Faculty Opinions recommendation of The different extent of B and T cell immune reconstitution after hematopoietic stem cell transplantation and enzyme replacement therapies in SCID patients with adenosine deaminase deficiency.

Author(s):  
Francisco A Bonilla
2002 ◽  
Vol 55 (7-8) ◽  
pp. 293-298 ◽  
Author(s):  
Svetlana Vojvodic

Introduction Despite engraftment and function of graft after hematopoietic stem cell transplantation severe immune suppression is a characteristic of early posttransplant period. Primary parameters contributing to posttransplant immunoincompetence include: lack of sustained transfer of donor antigen specific immunity, recapitulation of immunological ontogeny effect of graft-versus-host disease (GvHD) and its therapy and reduction of the recipient's thymic function. Normal immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) Immune reconstitution following allogeneic HSCT depends on the age of recipient initial pathology, degree of HLA and minor histocompatibility antigen mismatches, T-cell depletion and use of anti-T-cell antibodies for conditioning and prevention of GvHD, posttransplant complications such as acute and chronic GvHD, relapse of disease and infectious status of the donor and recipient prior to transplantation. Tests for studying immune reconstitution following allogeneic transplantation most often used are cutaneous tests of delayed hypersensitivity, phenotyping of blood mononuclear cells and investigation of their functions, production of antibodies (IgG, IgM and IgA) and cytokines such as IL-2, TGF-a, TNF-a or IL-10, study of TCR, mixed leukocyte reaction toward allogeneic cells CD4/CD8 ratio and others. New tools for assessment of immune reconstitution after HSCT New methods and techniques for monitoring immune reconstitution are as follows: ELISPOT assay quantifies secretion of cytokines by T lymphocytes, analysis of the T-cell receptor (chain diversity during immune reconstitution by IMMUNOSCOPE/SPECTRATYPING method, and TREC technology that detects recent thymic emigrants in peripheral blood. Conclusion Usage of above-mentioned contemporary techniques makes it possible to assess and monitor the dynamics of immune reconstitution especially reconstitution of T-cell diversity, thymic function and antigen-specific T-cell response following HSCT.


Blood ◽  
2012 ◽  
Vol 120 (9) ◽  
pp. 1820-1830 ◽  
Author(s):  
Luca Vago ◽  
Giacomo Oliveira ◽  
Attilio Bondanza ◽  
Maddalena Noviello ◽  
Corrado Soldati ◽  
...  

Abstract The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell–depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+-cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.


2005 ◽  
Vol 80 (5) ◽  
pp. 673-682 ◽  
Author(s):  
Tiziana Benicchi ◽  
Claudia Ghidini ◽  
Alessandro Re ◽  
Chiara Cattaneo ◽  
Salvatore Casari ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document