Thymic-deficient hosts rely primarily on antigen-driven expansion to restor
e the peripheral T-cell compartment following T-cell depletion (TCD), The d
egree to which this thymic-independent pathway can restore immune competenc
e remains poorly understood but has important implications for a number of
clinical conditions including stem cell transplantation and human immunodef
iciency virus (HIV) infection. A model of MY-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 x 10(6) lym
ph node (LN) cells representing approximately 10% of the T-cell repertoire,
Constitutive expression of bcl-2 in the expanding inocula restored recall
responses to MY at a substantially lower LN cell dose (1 x 10(6)), which is
normally insufficient to induce MY-mediated graft rejection in athymic hos
ts. Interestingly, bcl-2 had no effect on primary responses. Interleukin-7
(IL-7) potently enhanced thymic-independent peripheral expansion and led to
MY graft rejection using an LN cell dose of 1 x 10(6) 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, improve
d 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 a
s a potent modulator of thymic-independent T-cell regeneration. (Blood. 200
1;97:1525-1533) (C) 2001 by The American Society of Hematology.