Nitric oxide-independent CTL suppression during tumor progression: association with arginase-producing (M2) myeloid cells.
Most of the mice bearing a s.c. BW-Sp3 lymphoma tumor mount a CD8(+) T cell-mediated response resulting in tumor regression. Nonetheless, tumor progression occurs in some of the recipients and is associated with CTL inactivity. We demonstrated that T cell-activating APC were induced in regressors whereas T cell suppressive myeloid cells predominated in the spleen of progressors. Indeed, in vitro depletion of either the adherent or the CD11b(+) populations restored T cell cytotoxicity and proliferation in these mice. This CTL inhibition was cell-to-cell contact-dependent but not mediated by NO. However, the same progressor suppressive cells prevented the activity of in vitro-restimulated CTLs derived from regressors in a cell-to-cell contact and NO-dependent fashion. Thus, either the NO-dependent or -independent suppressive pathway prevailed, depending on the target CTL population. In addition, the suppressive population expressed a high arginase activity, suggesting an association of the suppressive phenotype with alternatively activated (M2) myeloid cells. However, the high arginase activity is not directly involved in the suppressive process. Our results provide new insights for myeloid cell-mediated CTL inhibition during cancer progression.
Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Belgium. tmliuyua@vub.ac.be
Yuanqing
Y
Liu
Jo A
JA
Van Ginderachter
Lea
L
Brys
Patrick
P
De Baetselier
Geert
G
Raes
Anja B
AB
Geldhof
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001119:Arginase / Q000096:biosynthesis*; D039481:CD11b Antigen / Q000096:biosynthesis; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D016130:Immunophenotyping; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D022423:Myeloid Cells / Q000201:enzymology* / Q000276:immunology*; D009569:Nitric Oxide / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D009569:Nitric Oxide; D001119:Arginase