Analysis of splenic Gr-1int immature myeloid cells in tumor-bearing mice.
It is known that the number of ImC, expressing myeloid markers, CD11b and Gr-1, increase with tumor growth and ImC play a role in the escape of tumor cells from immunosurveillance in tumor-bearing mice and cancer patients. However, the mechanisms by which ImC suppress immune responses in tumor-bearing mice have not been completely elucidated. In the present study, we investigated the function of splenic ImC freshly isolated from tumor-bearing mice and splenic ImC differentiated in vitro by GM-CSF. Freshly isolated splenic ImC were divided into two groups depending on Gr-1 expression, Gr-1 high (Gr-1hi) and intermediate (Gr-1int). Freshly isolated splenic Gr-1int ImC, but not Gr-1hi ImC, from tumor-bearing mice reduced production of IFN-gamma in CD8+ T cells, but neither splenic Gr-1int ImC nor Gr-1hi ImC isolated from naive mice did. Both Gr-1int and Gr-1hi ImC differentiated in vitro by GM-CSF inhibited production of IFN-gamma in both CD8+ and CD4+ T cells. In addition, the differentiated Gr-1int ImC, one-third of which were CD11c+F4/80+ cells, and their culture supernatants suppressed proliferative responses of T cells stimulated by CD3 ligation, but the differentiated Gr-1hi ImC and their culture supernatants did not. These results suggest that Gr-1int ImC are altered to immune-suppressive cells in tumor circumstances and that they are differentiated by GM-CSF progressively into CD11c+F4/80+ cells with further suppressive activity against T cells.
Yamamoto
Yoshiko
Y
Department of Pathology, Shiga University of Medical Science, Ohtsu, Japan.
Ishigaki
Hirohito
H
Ishida
Hideaki
H
Itoh
Yasushi
Y
Noda
Yoichi
Y
Ogasawara
Kazumasa
K
D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000737:chemistry* / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D019707:Receptors, Chemokine / Q000032:analysis*
D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D007371:Interferon-gamma