Anti-metastatic activity induced by the in vivo activation of purified protein derivative (PPD)-recognizing Th1 type CD4+ T cells.
The Th1 type Cd4+ T cell clone (MH2), which is capable of recognizing purified protein derivative from Mycobacterium tuberculosis (PPD), was examined for its anti-metastatic activity against melanoma. In using an in vitro proliferative assay, MH2 was able to recognize PPD-derived antigen in a major histocompatibility complex class II-restricted manner. MH2 showed neither any natural killer (NK) activity nor cytolytic activity against syngeneic B16 melanoma. This clone produced interferon-gamma, tumor necrosis factor and interleukin-2, but not interleukin-4, when co-cultured with PPD and irradiated syngeneic C57BL/6 spleen cells, suggesting that this clone could thus be assigned to the Th1 subset. An intraperitoneal (i.p.) co-injection of 2 x 10(6) MH2 and 50 micrograms PPD increased the NK activity of the peritoneal exudate cells (PEC) and the percentage of NK1.1+ cells in the PEC. These activated NK cells showed a low but significantly cytolytic activity against B16 melanoma. The augmented NK activity induced by the co-injection of MH2 and PPD was maintained by the weekly additional i.p. injections of PPD alone. Using a murine metastatic model, and i.p. co-injection of MH2 and PPD-induced anti-metastatic activity against B16 melanoma. This anti-metastatic activity was then abrogated by the in vivo administration of anti-asialo GM1 serum. In addition, the NK activity in both peripheral blood and metastatic lungs was significantly augmented in the mice which were co-injected with MH2 and PPD. Taken together, these findings indicate that the in vivo activation of Th1 type CD4+ T cells augmented the NK activity in vivo and thus could potentially be an efficient immunotherapeutic weapon against metastasis of melanoma. These results also imply that adoptive immunotherapy could induce anti-metastatic activity through cytokine production but not through any direct cytolytic activity.
Department of Immunology, Kyushu University, Japan.
Y
Y
Shinomiya
M
M
Harada
S
S
Kurosawa
T
T
Okamoto
H
H
Terao
G
G
Matsuzaki
T
T
Shirakusa
K
K
Nomoto
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002999:Clone Cells / Q000276:immunology / Q000637:transplantation; D003601:Cytotoxicity Tests, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016219:Immunotherapy, Adoptive; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000187:drug effects; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects*; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D012515:Mast-Cell Sarcoma; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D014373:Tuberculin / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D014373:Tuberculin; D007371:Interferon-gamma