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Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells
Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells
- Source :
- Nature Medicine. 11:1238-1243
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- CD4(+)CD25(+) regulatory T (T(reg)) cells have a crucial role in maintaining immune tolerance. Mice and humans born lacking T(reg) cells develop severe autoimmune disease, and depletion of T(reg) cells in lymphopenic mice induces autoimmunity. Interleukin (IL)-2 signaling is required for thymic development, peripheral expansion and suppressive activity of T(reg) cells. Animals lacking IL-2 die of autoimmunity, which is prevented by administration of IL-2-responsive T(reg) cells. In light of the emerging evidence that one of the primary physiologic roles of IL-2 is to generate and maintain T(reg) cells, the question arises as to the effects of IL-2 therapy on them. We monitored T(reg) cells during immune reconstitution in individuals with cancer who did or did not receive IL-2 therapy. CD4(+)CD25(hi) cells underwent homeostatic peripheral expansion during immune reconstitution, and in lymphopenic individuals receiving IL-2, the T(reg) cell compartment was markedly increased. Mouse studies showed that IL-2 therapy induced expansion of existent T(reg) cells in normal hosts, and IL-2-induced T(reg) cell expansion was further augmented by lymphopenia. On a per-cell basis, T(reg) cells generated by IL-2 therapy expressed similar levels of FOXP3 and had similar potency for suppression compared to T(reg) cells present in normal hosts. These studies suggest that IL-2 and lymphopenia are primary modulators of CD4(+)CD25(+) T(reg) cell homeostasis.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Interleukin 2
Adolescent
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
T-Lymphocytes, Regulatory
General Biochemistry, Genetics and Molecular Biology
Immune tolerance
Autoimmunity
Mice
Immune system
immune system diseases
Lymphopenia
hemic and lymphatic diseases
medicine
Animals
Homeostasis
Humans
IL-2 receptor
Child
Mice, Knockout
Autoimmune disease
Interleukin
FOXP3
Forkhead Transcription Factors
Receptors, Interleukin-2
Sarcoma
hemic and immune systems
General Medicine
Middle Aged
medicine.disease
Recombinant Proteins
Mice, Inbred C57BL
Lymphocyte Transfusion
Immunology
Interleukin-2
Female
medicine.drug
Subjects
Details
- ISSN :
- 1546170X and 10788956
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Nature Medicine
- Accession number :
- edsair.doi.dedup.....e0787a5bee1533246b56a9c2650ea983
- Full Text :
- https://doi.org/10.1038/nm1312