Immunologic reconstitution after hematopoietic stem cell transplantation--parameters of monitoring and current methods of its evaluation

Abstract

Despite engraftment and function of graft after hematopoietic stem cell transplantation severe immune suppression is a characteristics of early posttransplant period. Primary parameters contributing to posttransplant immuno-incompetence 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. 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-alpha, TNF-alpha or IL-10, study of TCR, mixed leukocyte reaction toward allogeneic cells, CD4/CD8 ratio and others. New methods and techniques for monitoring immune reconstitution are as follows: ELISPOT assay qantifies 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. 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.