T cell immune reconstitution following lymphodepletion.
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.
Williams
Kirsten M
KM
Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Hakim
Frances T
FT
Gress
Ronald E
RE
D000818:Animals; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000209:etiology; D006706:Homeostasis; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D038041:Lymphopoiesis; D013601:T-Lymphocytes / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D019409:Interleukin-15; D015851:Interleukin-7; D016212:Transforming Growth Factor beta