T cell immune reconstitution following lymphodepletion
KM Williams, FT Hakim, RE Gress - Seminars in immunology, 2007 - Elsevier
KM Williams, FT Hakim, RE Gress
Seminars in immunology, 2007•ElsevierT cell reconstitution following lymphopenia from chemotherapy or stem cell transplant is
often slow and incompetent, contributing to the development of infectious diseases, relapse,
and graft-versus-host disease. This is due to the fact that de novo T cell production is
impaired following cytoreductive regimens. T cells can be generated from two pathways:(1)
thymus derived through active thymopoiesis and (2) peripherally expanded clones through
homeostatic proliferation. During recovery from lymphopenia, the thymic pathway is …
often slow and incompetent, contributing to the development of infectious diseases, relapse,
and graft-versus-host disease. This is due to the fact that de novo T cell production is
impaired following cytoreductive regimens. T cells can be generated from two pathways:(1)
thymus derived through active thymopoiesis and (2) peripherally expanded clones through
homeostatic proliferation. During recovery from lymphopenia, the thymic pathway is …
T cell reconstitution following lymphopenia from chemotherapy or stem cell transplant is often slow and incompetent, contributing to the development of infectious diseases, relapse, and graft-versus-host disease. This is due to the fact that de novo T cell production is impaired following cytoreductive regimens. T cells can be generated from two pathways: (1) thymus derived through active thymopoiesis and (2) peripherally expanded clones through homeostatic proliferation. During recovery from lymphopenia, the thymic pathway is commonly compromised in adults and T cells rely upon peripheral expansion to restore T cell numbers. This homeostatic proliferation exploits the high cytokine levels following lymphopenia to rapidly generate T cells in the periphery. Moreover, this early peripheral expansion of T cells can also be driven by exogenous antigen. This results in loss of T cell repertoire diversity and may predispose to auto- or allo-immunity. Alternatively, the high homeostatic proliferation following lymphopenia may facilitate expansion of anti-tumor immunity. Murine and human studies have provided insight into the cytokine and cellular regulators of these two pathways of T cell generation and the disparate portraits of T cell immunity created through robust thymopoiesis or peripheral expansion following lymphopenia. This insight has permitted the manipulation of the immune system to maximize anti-tumor immunity through lymphopenia and led to an appreciation of mechanisms that underlie graft versus host disease.
Elsevier