Journal of Experimental Medicine, Vol 149, 185-199, Copyright © 1979 by Rockefeller University Press
Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. III. Amplification of a generation of tumor-specific killer T-lymphocyte activities by suppressor T-cell-depleted hapten- reactive T lymphocytes
T Hamaoka, H Fujiwara, K Teshima, H Aoki, H Yamamoto and M Kitagawa
2,4.6-trinitrophenyl (TNP)-reactive T-cell activities were raised in mice
by immunization with TNP-isologous mouse gamma globulin. After establishing
that TNP-reactive T lymphocytes can serve as amplifier cells for induction
of killer T lymphocytes in allogeneic system, we explored the possibility
of this hapten-reactive T-cell system to amplify tumor-specific killer
T-lymphocyte activity in the syngeneic system. We utlized relatively weak
immunogenic syngeneic plasmacytoma X5563 in C3H/He mice. Analysis of the
TNP-reactive T-cell activities revealed that such T lymphocytes express the
biological functions of both major subtypes of regulatory T cells, namely
suppressors and helpers, and that TNP-reactive suppressor and helper T
lymphocytes, respectively, differ in their relative susceptibility to
specific inactivation by TNP conjugates of the nonimmunogenic D-amino acid
copolymer, D-glutamic acid, and D-lysine (D-GL). By taking advantage of the
relative susceptibility-difference to TNP-D-GL, selective inactivation of
TNP-reactive suppressor T cells was induced by appropriate treatment with
TNP-D-GL, and the generation of TNP-reactive helper T-cell activity was
amplified. The supplement of augmented TNP- reactive helper T-cell activity
to the system at the immunization with syngeneic X5563 with
TNP-haptenation, resulted in a striking augmentation of induction of
tumor-specific killer T-lymphocyte activity, and a considerable number of
hosts survived after the challenge with lethal dose of viable tumor cells.
Thus, appropriate manipulations designed to induce potent hapten-reactive
helper T- lymphocytes provided the potential for a very effective mode of
immunoprophylaxis against tumor.
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