Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T-cell activation events.
Eur J Immunol
; 43(11): 2930-42, 2013 Nov.
Article
en En
| MEDLINE
| ID: mdl-23878002
ABSTRACT
Tumor growth coincides with an accumulation of myeloid-derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b(+) CD115(+) Ly6G(-) Ly6C(high) MDSCs and granulocytic CD11b(+) CD115(-) Ly6G(+) Ly6C(int) polymorphonuclear (PMN)-MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8(+) 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 CD8(+) 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-MDSCs affect IL-2Rα (CD25) expression and STAT-5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN-γ production by CD8(+) T cells on a per cell basis, illustrating that some T-cell activation characteristics are actually stimulated by MDSCs. Conversely, MO-MDSCs counteract the activation-induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8(+) T-cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL-mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8(+) T-cell activation events in vitro, whereby some parameters are suppressed while others are stimulated.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
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Linfocitos T CD8-positivos
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Células Mieloides
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Neoplasias
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Bélgica