Immunosurveillance of Erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance.
To assess the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in overcoming immunosurveillance of Erbb2 (HER-2/neu) mammary lesions, we studied the effects of their sustained removal in BALB/c female mice made transgenic for the rat Erbb2 (r-Erbb2) oncogene (BALB-neuT mice), which develop multiple mammary carcinomas. During the progression of these lesions, Treg cells expand in the spleen, tumor draining lymph nodes, and tumors. Repeated administration of anti-CD25 antibodies extends tumor-free survival, reduces carcinoma multiplicity, and leads to the manifestation of a natural antibody and CTL-mediated reactivity against r-Erbb2. Loss of Foxp3(+) Treg cells during anti-CD25 treatment remarkably caused the disappearance of Gr1(+) immature myeloid cells, suggesting a cross-talk between these two inhibitory immune cell types. Treg cell expansion associated with r-Erbb2 overexpression may be seen as a physiologic response to dampen the immune reaction elicited by local anomalous overexpression of a self-antigen.
Ambrosino
Elena
E
Department of Clinical and Biological Sciences, University of Turin, Ospedale San Luigi Gonsaga, I-10043 Orbassano, Italy.
Spadaro
Michela
M
Iezzi
Manuela
M
Curcio
Claudia
C
Forni
Guido
G
Musiani
Piero
P
Wei
Wei-Zen
WZ
Cavallo
Federica
F
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007074:Immunoglobulin G; D018719:Erb-b2 Receptor Tyrosine Kinases; D015375:Receptors, Interleukin-2