An efficient Th2-type memory follows CD8+ lymphocyte-driven and eosinophil-mediated rejection of a spontaneous mouse mammary adenocarcinoma engineered to release IL-4.
A retroviral infection was used to introduce the cDNA coding for mouse IL-4 into the parental cells of a spontaneous adenocarcinoma of BALB/c mice (TS/A-pc). Four clones releasing between 5 to 40 U of IL-4 (10(5) cells) in 48 h culture were selected. The secretion of IL-4 does not affect their in vitro growth, whereas their ability to form tumor in vivo inversely correlates with the amount of IL-4 secreted. Although morphologic observation suggested that the rejection of clone D5.40 cells (releasing 40 U of IL-4) depends on eosinophil cytolysis, lymphocyte depletion experiments showed that this required CD8+ lymphocyte guidance. Mice that had rejected D5.40 cells were immune to a subsequent challenge with TS/A-pc. This memory rests on the interaction between noncytotoxic lymphocytes, eosinophils, and IgG1 and IgE anti-TS/A Abs. Comparison of these memory mechanisms with those elicited by IL-2 gene-transduced TS/A cells shows that the kind of cytokine released by the tumor cells determines the type of response. This Th2 memory seems to be more efficient in protecting against a subsequent challenge of TS/A-pc than the Th1-type memory elicited by IL-2 gene-transduced TS/A cells.
Pericle
F
F
CNR Center for Immunogenetics and Experimental Oncology University of Turin, Italy.
Giovarelli
M
M
Colombo
M P
MP
Ferrari
G
G
Musiani
P
P
Modesti
A
A
Cavallo
F
F
Di Pierro
F
F
Novelli
F
F
Forni
G
G
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000276:immunology; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000096:biosynthesis*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D015847:Interleukin-4