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

Abstract

CD4+ T cells can recognize a processed idiotypic peptide derived from the mouse lambda 2(315) immunoglobulin light chain. The idiotypic peptide is presented on the I-E(d) class II major histocompatibility complex molecule. Mice made transgenic for a lambda 2(315)-specific alpha beta T cell receptor have been demonstrated to be specifically resistant against a tumor challenge with the MOPC315 (alpha,lambda 2(315)) 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) alpha 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 alpha beta 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 alpha-chain genes, are both dispensable for effective immunosurveillance in our system. Surprisingly, we found that transgenic CD8+ and CD4-8- cells are idiotype-specific and I-E(d) 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.

Transfer of idiotypic protein primed allogeneic marrow grafts elicits potent graft-versus-myeloma effects in mice

“…16,26 Bogen et al 26 reported that id-specific CD4 ϩ T cells can protect against challenges with small numbers of the MOPC315 plasmocytoma. On the other hand, Ö sterborg et al 27 detected both CD4 ϩ and CD8 ϩ idiotype T cell reactivity in early stage myeloma patients following id-protein vaccination.…”

Efficient Delivery of T Cell Epitopes to APC by Use of MHC Class II-Specific Troybodies

“…Mice BALB/cABom, C.B-17/lcrBom, C57BL/6JBom, C3H/HeJBom, SCID on C.B-17 background, and the 2 315 -specific TCR-transgenic mice on a C.B-17-SCID background (15) were all from M&B (Ry, Denmark). The 2 315 -specific TCR-transgenic mice on BALB/c background (16) and the 2 315 -specific TCR-transgenic mice on a Rag2 Ϫ/Ϫ BALB/c background (unpublished) were bred in our animal facility.…”

Idiotype protein-pulsed dendritic cells produce strong anti-myeloma effects after syngeneic stem cell transplantation in mice

“…[9][10][11][12]17 In spite of the fact that the vast majority of myelomas failed to express MHC class II molecules, CD4 + T cells may play an important role in tumour immunity. Qin and Blankenstein 31 recently showed that cellular immunity against MHC class II negative tumours can be mediated by CD4 + T cells through an IFN-␥-dependent mechanism.…”

“…These findings could be confirmed in several other B cell tumour models. [7][8][9] In most of these studies, anti-Id immunity was dependent on T cells rather than on anti-Id antibodies. Bogen et al have shown that Id-specific CD4 + T cells are essential for tumour protection in the MOPC myeloma model.…”

“…Bogen et al have shown that Id-specific CD4 + T cells are essential for tumour protection in the MOPC myeloma model. [9][10][11][12] Several experimental and clinical data suggest that dendritic cells (DC) specialised to optimally present antigens can be used to enhance the antitumour T cell response. [13][14][15][16][17][18] In a murine B cell lymphoma model, Flamand et al 16 have shown that a specific anti-Id immunity can be generated in the host by immunisation with DC loaded in vitro with the Id protein.…”