Interleukin-7 restores immunity in athymic T-cell-depleted hosts

Terry J. Fry, Barbara L. Christensen, Kristin L. Komschlies, Ronald E. Gress, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

Thymic-deficient hosts rely primarily on antigen-driven expansion to restore the peripheral T-cell compartment following T-cell depletion (TCD). The degree to which this thymic-independent pathway can restore immune competence remains poorly understood but has important implications for a number of clinical conditions including stem cell transplantation and human immunodeficiency virus (HIV) infection. A model of HY-mediated skin graft rejection by athymic, TCD mice was used to show that restoration of naive and recall responses via peripheral expansion requires transfer of only 25 × 106 lymph node (LN) cells representing approximately 10% of the T-cell repertoire. Consitutive expression of bcl-2 in the expanding inocula restored recall responses to HY at a substantially lower LN cell dose (1 × 106), which is normally insufficient to induce HY-mediated graft rejection in athymic hosts. Interestingly, bcl-2 had no effect on primary responses. Interleukin-7 (IL-7) potently enhanced thymic-independent peripheral expansion and led to HY graft rejection using an LN cell dose of 1 × 106 in both primary and recall models. The restoration of immune competence by IL-7 appeared to be mediated through a combination of programmed cell death inhibition, improved costimulation, and modulation of antigen-presenting cell (APC) function. These results show that immune competence for even stringent antigens such as HY can be restored in the absence of thymic function and identify IL-7 as a potent modulator of thymic-independent T-cell regeneration.

Original languageEnglish (US)
Pages (from-to)1525-1533
Number of pages9
JournalBlood
Volume97
Issue number6
DOIs
StatePublished - Mar 15 2001

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Fry, T. J., Christensen, B. L., Komschlies, K. L., Gress, R. E., & Mackall, C. L. (2001). Interleukin-7 restores immunity in athymic T-cell-depleted hosts. Blood, 97(6), 1525-1533. https://doi.org/10.1182/blood.V97.6.1525