T cell immune reconstitution following lymphodepletion

Semin Immunol. 2007 Oct;19(5):318-30. doi: 10.1016/j.smim.2007.10.004. Epub 2007 Nov 19.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / physiology
  • Cytotoxicity, Immunologic
  • Graft vs Host Disease / etiology
  • Homeostasis
  • Humans
  • Interleukin-15 / pharmacology
  • Interleukin-7 / pharmacology
  • Lymphocyte Activation
  • Lymphocyte Depletion*
  • Lymphopoiesis
  • T-Lymphocytes / physiology*
  • T-Lymphocytes, Regulatory / physiology
  • Thymus Gland / physiology
  • Transforming Growth Factor beta / pharmacology


  • Cytokines
  • Interleukin-15
  • Interleukin-7
  • Transforming Growth Factor beta