Interleukin-7 restores immunity in athymic T-cell-depleted hosts.
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 x 10(6) lymph node (LN) cells representing approximately 10% of the T-cell repertoire. Constitutive expression of bcl-2 in the expanding inocula restored recall responses to HY at a substantially lower LN cell dose (1 x 10(6)), 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 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, 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.
Fry
T J
TJ
Molecular Oncology Section, Pediatric Branch, National Cancer Institute, National Institutes of Heath, Bethesda, Maryland, USA. tf60y@nih.gov
Christensen
B L
BL
Komschlies
K L
KL
Gress
R E
RE
Mackall
C L
CL
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D007107:Immune System / Q000166:cytology / Q000187:drug effects*; D007114:Immunization / Q000009:adverse effects; D016867:Immunocompromised Host / Q000187:drug effects*; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000637:transplantation; D008212:Lymphocyte Depletion / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*; D013934:Thymectomy / Q000009:adverse effects / Q000534:rehabilitation
D015851:Interleukin-7