ANTITUMOR-ACTIVITY OF IDIOTYPE-SPECIFIC, MHC-RESTRICTED TH1 AND TH2 CLONES INVITRO AND INVIVO

Idiotypes (Id) can serve as individual markers on B cells; therefore, cytotoxic Id-specific T cells may play a significant role in immunological surveillance of Id+ B-cell tumours. We have investigated the anti-tumour activity of CD4+ BALB/c Th1 and Th2 clones which recognize a processed Id of the syngeneic lambda2(315) L chain in the context of the class II MHC molecule I-E(d). Id-specific T cells and A20/46 B lymphoma cells transfected with the lambda2(315) gene were injected s.c. into the same site of BALB/c mice (Winn assay). The results show that both Th1 and Th2 clones can protect against tumour development. The protection was Id-specific because T cells did not influence tumour development by an A20/46 B lymphoma cell line transfected with the pSV2neo expression vector alone. In vitro studies showed that the Th1 clones were cytotoxic to lambda2(315)-transfected B lymphoma cells; by contrast, the Th2 clone was not cytotoxic in Cr-51-release assay even though the Th2 cells inhibited the growth of lambda2(315) B lymphoma cells. The anti-lymphoma properties of both the Th1 and Th2 clones appear to involve as yet undefined cytotoxic and growth inhibiting molecules.