Gf. Lauritzsen et al., NAIVE IDIOTYPE-SPECIFIC CD4-CELLS AND IMMUNOSURVEILLANCE OF B-CELL TUMORS( T), Proceedings of the National Academy of Sciences of the United Statesof America, 91(12), 1994, pp. 5700-5704
The immunosurveillance hypothesis suggests that lymphocytes can recogn
ize tumor-specific antigens expressed by transformed cells and initiat
e their elimination. Immunosurveillance implies that lymphocytes of na
ive phenotype can home to a tumor site and become activated by tumor-s
pecific antigens. In this study, we have employed T-cell receptor tran
sgenic mice as a source of naive, tumor-specific T cells. The transgen
ic, CD4(+) T cells recognize a 91- to 101-residue fragment of the lamb
da 2(315) immunoglobulin light chain presented by I-E(d) class II mole
cules. Such naive, idiotype-specific, CD4(+) T cells protected against
tumor development of a class II negative plasmacytoma (MOPC315) and a
class II positive B lymphoma (F9), which both secrete lambda 2(315) i
mmunoglobulin. Adoptive transfer experiments demonstrated that 2 x 10(
6) lymph node cells were sufficient for protection against MOPC315. De
pletion of T-cell subsets indicated that transgenic CD4(+) cells were
indispensable for tumor resistance. However, an additional role of CD8
(+) T cells is not ruled out. In contrast to the resistance against th
e secreting MOPC315 and F9 cells, transgenic mice were not protected a
gainst B lymphoma cells (F67), which do not secrete lambda 2(315) but
express a truncated lambda 2(315) chain intracellularly. The results s
uggest that lambda 2(315) is processed and presented by host antigen-p
resenting cells, which in turn activate naive, idiotype-specific T cel
ls.