Abstract
Both thymic and extrathymic T lineage development are characterized by cytokine-dependent regulation of complex proliferative, differentiative, and anti-apoptotic processes. The role of the γc-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, through the analysis of double knock-out mice, which lack signaling through the IL-7R and other γc-dependent cytokines, we revealed a role for IL-15 in the production of early thymic pro-T cells. Although IL-2 does not function in the production of thymocytes, thymic restoration of IL-2R expression prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mice, suggesting that IL-2R functions non-redundantly at the level of the thymus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also extend their developmental effects beyond the thymus to other sites of T lymphocyte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically diverse subsets of intestinal intraepithelial lymphocytes. (C) 2000 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 465-474 |
| Number of pages | 10 |
| Journal | Seminars in Immunology |
| Volume | 12 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 13 2000 |
Fingerprint
Keywords
- Development
- IL-15
- IL-2
- IL-7
- T cell
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
Thymic and intestinal intraepithelial T lymphocyte development are each regulated by the γc-dependent cytokines IL-2, IL-7, and IL-15. / Porter, Brian O.; Malek, Thomas.
In: Seminars in Immunology, Vol. 12, No. 5, 13.11.2000, p. 465-474.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thymic and intestinal intraepithelial T lymphocyte development are each regulated by the γc-dependent cytokines IL-2, IL-7, and IL-15
AU - Porter, Brian O.
AU - Malek, Thomas
PY - 2000/11/13
Y1 - 2000/11/13
N2 - Both thymic and extrathymic T lineage development are characterized by cytokine-dependent regulation of complex proliferative, differentiative, and anti-apoptotic processes. The role of the γc-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, through the analysis of double knock-out mice, which lack signaling through the IL-7R and other γc-dependent cytokines, we revealed a role for IL-15 in the production of early thymic pro-T cells. Although IL-2 does not function in the production of thymocytes, thymic restoration of IL-2R expression prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mice, suggesting that IL-2R functions non-redundantly at the level of the thymus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also extend their developmental effects beyond the thymus to other sites of T lymphocyte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically diverse subsets of intestinal intraepithelial lymphocytes. (C) 2000 Academic Press.
AB - Both thymic and extrathymic T lineage development are characterized by cytokine-dependent regulation of complex proliferative, differentiative, and anti-apoptotic processes. The role of the γc-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, through the analysis of double knock-out mice, which lack signaling through the IL-7R and other γc-dependent cytokines, we revealed a role for IL-15 in the production of early thymic pro-T cells. Although IL-2 does not function in the production of thymocytes, thymic restoration of IL-2R expression prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mice, suggesting that IL-2R functions non-redundantly at the level of the thymus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also extend their developmental effects beyond the thymus to other sites of T lymphocyte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically diverse subsets of intestinal intraepithelial lymphocytes. (C) 2000 Academic Press.
KW - Development
KW - IL-15
KW - IL-2
KW - IL-7
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=0033744745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033744745&partnerID=8YFLogxK
U2 - 10.1006/smim.2000.0264
DO - 10.1006/smim.2000.0264
M3 - Article
C2 - 11085179
AN - SCOPUS:0033744745
VL - 12
SP - 465
EP - 474
JO - Seminars in Immunology
JF - Seminars in Immunology
SN - 1044-5323
IS - 5
ER -