| First Author | Uddin MN | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 4 | Pages | 1946-53 |
| PubMed ID | 24446520 | Mgi Jnum | J:209353 |
| Mgi Id | MGI:5567012 | Doi | 10.4049/jimmunol.1301976 |
| Citation | Uddin MN, et al. (2014) TNF-alpha-dependent hematopoiesis following Bcl11b deletion in T cells restricts metastatic melanoma. J Immunol 192(4):1946-53 |
| abstractText | Using several tumor models, we demonstrate that mice deficient in Bcl11b in T cells, although having reduced numbers of T cells in the peripheral lymphoid organs, developed significantly less tumors compared with wild-type mice. Bcl11b(-/-) CD4(+) T cells, with elevated TNF-alpha levels, but not the Bcl11b(-/-) CD8(+) T cells, were required for the reduced tumor burden, as were NK1.1(+) cells, found in increased numbers in Bcl11b(F/F)/CD4-Cre mice. Among NK1.1(+) cells, the NK cell population was predominant in number and was the only population displaying elevated granzyme B levels and increased degranulation, although not increased proliferation. Although the number of myeloid-derived suppressor cells was increased in the lungs with metastatic tumors of Bcl11b(F/F)/CD4-Cre mice, their arginase-1 levels were severely reduced. The increase in NK cell and myeloid-derived suppressor cell numbers was associated with increased bone marrow and splenic hematopoiesis. Finally, the reduced tumor burden, increased numbers of NK cells in the lung, and increased hematopoiesis in Bcl11b(F/F)/CD4-Cre mice were all dependent on TNF-alpha. Moreover, TNF-alpha treatment of wild-type mice also reduced the tumor burden and increased hematopoiesis and the numbers and activity of NK cells in the lung. In vitro treatment with TNF-alpha of lineage-negative hematopoietic progenitors increased NK and myeloid differentiation, further supporting a role of TNF-alpha in promoting hematopoiesis. These studies reveal a novel role for TNF-alpha in the antitumor immune response, specifically in stimulating hematopoiesis and increasing the numbers and activity of NK cells. |
