ANTIMETASTATIC ACTIVITY-INDUCED BY THE IN-VIVO ACTIVATION OF PURIFIEDPROTEIN DERIVATIVE (PPD)-RECOGNIZING TH1 TYPE CD4(+)T CELLS

The Th1 type CD4(+) T cell clone (MH2), which is capable of recognizin g purified protein derivative from Mycobacterium tuberculosis (PPD), w as examined for its anti-metastatic activity against melanoma. In usin g an in vitro proliferative assay, MH2 was able to recognize PPD-deriv ed antigen in a major histocompatibility complex class II-restricted m anner. MH2 showed neither any natural killer (NK) activity nor cytolyt ic activity against syngeneic B16 melanoma. This clone produced interf eron-gamma, tumor necrosis factor and interleukin-2, but not interleuk in-4, when co-cultured with PPD and irradiated syngeneic C57BL/6 splee n 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 mu g PPD increased the NK activity of the peritoneal exudate cells (P EG) and the percentage of NK1.1(+) cells in the PEG. These activated N K cells showed a low but significant cytolytic activity against B16 me lanoma. The augmented NK activity induced by the co-injection of MH2 a nd PPD was maintained by the weekly additional i.p. injections of PPD alone. Using a murine metastatic model, an i.p. co-injection of MH2 an d PPD-induced antimetastatic activity against B16 melanoma. This anti- metastatic activity was then abrogated by the in vivo administration o f anti-asialo GM1 serum. In addition, the NK activity in both peripher al blood and metastatic lungs was significantly augmented in the mice which were co-injected with MH2 and PPD. Taken together, these finding s indicate that the in vivo activation of Th1 type CD4(+) T cells augm ented the NK activity in vivo and thus could potentially be an efficie nt immunotherapeutic weapon against metastasis of melanoma. These resu lts also imply that adoptive immunotherapy could induce antimetastatic activity through cytokine production but not through anp direct cytol ytic activity.