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Contrasuppression and tumor rejection
P M Flood1, A Friedman, B Horvat
1Laboratory of Cellular Immunology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06518.
Abstract:
The growth of a highly progressive MCA-induced tumor 3152-PRO is dependent on the activity of suppressor T cells (Ts). Injection of syngeneic mice with antibodies specific for Ts leads to enhanced tumor transplantation resistance of the 3152-PRO tumor. In addition, injection of recipient mice with highly immunogenic regressor tumors conjugated with trinitrophenyl (TNP) activates a T cell population which also mediates protection to transplantation of TNP-conjugated 3152-PRO tumor cells. One such tumor, 1591-RE, was investigated in detail to determine the phenotype and biologic activity of this T cell population in overcoming Ts cell activity. Induction of transplantation resistance requires the presence of TNP hapten on both the highly regressive immunizing tumor (and not its progressor variant 1591-PRO4), and on the challenge tumor 3152-PRO. The cell population from TNP-1591-RE immunized animals which mediates protection against the transplantation of TNP-3152-PRO is Thy-1+, CD4+, 8-, Lyt1+, I-J+, and Vicia villosa lectin adherent, the identical phenotype to antigen-specific contrasuppressor T cells in the contact sensitivity (CS) response to TNP in vivo. A T cell population of identical phenotype from TNP-1591-RE immunized mice can overcome the effects of antigen-specific Ts cells on PCl-immune cells in the adoptive transfer of CS in vivo. These results suggest that immunoregulatory cells that mediate protection against progressive tumors may be identical in function to antigen-specific contrasuppressor T cells.
Insights
Tumor growth is controlled by suppressor T cells (Ts). Activating specific T cells with a trinitrophenyl (TNP) conjugated tumor can overcome this suppression, offering a potential strategy for cancer immunotherapy.
Area of Science:
- Immunology
- Cancer Biology
- T Cell Regulation
Background:
- Progressive tumor growth, such as the MCA-induced 3152-PRO tumor, is often facilitated by the activity of suppressor T cells (Ts).
- Overcoming Ts cell activity is crucial for enhancing anti-tumor immunity and transplantation resistance.
Purpose of the Study:
- To investigate the phenotype and biologic activity of T cells capable of overcoming Ts cell-mediated suppression in a progressive tumor model.
- To determine if these T cells are functionally identical to antigen-specific contrasuppressor T cells involved in other immune responses.
Main Methods:
- Mice were immunized with highly immunogenic regressor tumors conjugated with trinitrophenyl (TNP).
- The protective T cell population's phenotype was analyzed using flow cytometry and lectin adherence assays.
- The ability of these T cells to overcome Ts cell activity was assessed in tumor transplantation and adoptive transfer models of contact sensitivity.
Main Results:
- Injection of TNP-conjugated regressor tumors activated a T cell population that conferred resistance to TNP-conjugated progressive tumor challenge.
- The protective T cell population exhibited a phenotype (Thy-1+, CD4+, 8-, Lyt1+, I-J+, Vicia villosa lectin adherent) identical to antigen-specific contrasuppressor T cells.
- These T cells were shown to overcome the suppressive effects of antigen-specific Ts cells in vivo.
Conclusions:
- The immunoregulatory cells mediating protection against progressive tumors share a functional identity with antigen-specific contrasuppressor T cells.
- This finding suggests a potential unified mechanism for immune regulation in both tumor immunity and other T cell-mediated responses.
- Targeting these contrasuppressor T cells could represent a novel therapeutic strategy for enhancing anti-tumor immunity.