Naive CD4+ T cells confer idiotype‐specific tumor resistance in the absence of antibodies

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Abstract
CD4+ T cells can recognize a processed idiotypic peptide derived from the mouse λ2315 immunoglobulin light chain. The idiotypic peptide is presented on the I‐Ed class II major histocompatibility complex molecule. Mice made transgenic for a λ2315‐specific αβ T cell receptor have been demonstrated to be specifically resistant against a tumor challenge with the MOPC315 (α, λ2315) plasmacytoma (Lauritzsen, G. F., Weiss, S., Dembic, Z. and Bogen, B., Proc. Natl. Acad. Sci. USA 1994. 91: 5700). That study, however, did not rule out a role of either anti‐Id antibodies or T cells expressing nontransgenic specificities due to expression of endogenous T cell receptor (TcR) α chains. Also, the role of different T cell subsets in protection was unclear. To remove these ambiguities, we have now made the transgenic mice homozygous for the scid mutation, known to inhibit both Ig and TcR gene rearrangements. Such transgenic SCID mice lack B cells and antibodies while they still have plenty of CD4+ and CD4−8− cells expressing the transgenic αβ T cell receptor. The number of CD8+ T cell is dramatically reduced. Even so, transgenic SCID mice are protected against a challenge with MOPC315 plasmacytoma cells. Therefore, B cells, as well as novel T cell receptor specificities created by rearrangements of endogenous α‐chain genes, are both dispensable for effective immunosurveillance in our system. Surprisingly, we found that transgenic CD8+ and CD4−8− cells are idiotypespecific and I‐Ed restricted. However, these T cell subsets are not required for resistance because adoptive transfer experiments demonstrated that highly purified transgenic SCID CD4+ cells suffice for tumor protection.

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