Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors.
The immunosurveillance hypothesis suggests that lymphocytes can recognize tumor-specific antigens expressed by transformed cells and initiate their elimination. Immunosurveillance implies that lymphocytes of naive phenotype can home to a tumor site and become activated by tumor-specific antigens. In this study, we have employed T-cell receptor transgenic mice as a source of naive, tumor-specific T cells. The transgenic, CD4+ T cells recognize a 91- to 101-residue fragment of the lambda 2(315) immunoglobulin light chain presented by I-Ed class II molecules. 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) immunoglobulin. Adoptive transfer experiments demonstrated that 2 x 10(6) lymph node cells were sufficient for protection against MOPC315. Depletion 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 the secreting MOPC315 and F9 cells, transgenic mice were not protected against B lymphoma cells (F67), which do not secrete lambda 2(315) but express a truncated lambda 2(315) chain intracellularly. The results suggest that lambda 2(315) is processed and presented by host antigen-presenting cells, which in turn activate naive, idiotype-specific T cells.
Lauritzsen
G F
GF
Institute of Immunology and Rheumatology, University of Oslo, Norway.
Weiss
S
S
Dembic
Z
Z
Bogen
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D015166:Monitoring, Immunologic; D010954:Plasmacytoma / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D016207:Cytokines; D007130:Immunoglobulin Idiotypes; D007146:Immunoglobulin lambda-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta