In:
The Journal of Immunology, The American Association of Immunologists, Vol. 177, No. 5 ( 2006-09-01), p. 3082-3088
Abstract:
TGF-β1 is present on cells derived from the microenvironment of human lung tumors and nonmalignant inflammatory tissues. We establish that this cell-associated cytokine mediates hyporesponsiveness of the memory T cells in these microenvironments in situ by blocking TCR signaling. T cells derived from these tissues failed to translocate NF-κB to the nucleus in response to CD3 + CD28 cross-linking. This nonresponsiveness was reversed by an anti-TGF-β1-neutralizing Ab. Refractoriness of the memory T cells to TCR activation was also reversed by the removal of TGF-β1 by briefly pulsing the cells in a low pH buffer. Addition of exogenous TGF-β1 to eluted T cells re-established their nonresponsive state. Neither TGF-β1, anti-TGF-β1 Ab, nor low pH affected TCR signaling potential of peripheral blood T cells. We conclude that TGF-β1 mediates a physiologically relevant regulatory mechanism, selective for memory T cells present in the tumor microenvironment and nonmalignant chronic inflammatory tissues.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.177.5.3082
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2006
detail.hit.zdb_id:
1475085-5
