In:
European Journal of Immunology, Wiley, Vol. 43, No. 11 ( 2013-11), p. 2930-2942
Abstract:
Tumor growth coincides with an accumulation of myeloid‐derived suppressor cells ( MDSC s), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD 11b + CD 115 + L y6 G − L y6 C high MDSC s and granulocytic CD 11b + CD 115 − L y6 G + L y6 C int polymorphonuclear (PMN)‐ MDSC s. However, whether these distinct MDSC subsets hamper all aspects of early CD 8 + T ‐cell activation — including cytokine production, surface marker expression, survival, and cytotoxicity — is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen‐driven CD 8 + T ‐cell proliferation, but differ in their dependency on IFN ‐γ, STAT ‐1, IRF ‐1, and NO to do so. Moreover, MO‐MDSC and PMN‐MDSCs diminish IL ‐2 levels, but only MO‐MDSC s affect IL ‐2 R α ( CD 25) expression and STAT ‐5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN ‐γ production by CD 8 + T cells on a per cell basis, illustrating that some T ‐cell activation characteristics are actually stimulated by MDSC s. Conversely, MO‐MDSC s counteract the activation‐induced change in CD 44, CD 62L, CD 162, and granzyme B expression, while promoting CD 69 and F as upregulation. Together, these effects result in an altered CD 8 + T ‐cell adhesiveness to the extracellular matrix and selectins, sensitivity to F asL‐mediated apoptosis, and cytotoxicity. Hence, MDSC s intricately influence different CD 8 + T ‐cell activation events in vitro, whereby some parameters are suppressed while others are stimulated.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201343349
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
1491907-2
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