Impaired immunological competence of spleen cells from neonatally thymectomized C57B1/6 young adult mice was apparent when these cells were tested in an in vitro graft-versus-host assay. Spleen cell inocula prepared from thymectomized mice did not induce enlargement of (C3H/eb x C57BI/6)F1 newborn spleen explants, whereas the same number of cells from intact donors consistently initiated splenomegaly. Spleen enlargement was observed, however, when the explants were challenged by cells from thymectomized donors in the presence of syngeneic thymus extract, indicating that the spleen cells in suspension attained immunological competence under the influence of a non-cellular component of the thymus. Immunocompetence was also evident when the cells from thymectomized donors were first incubated with thymus extract for 1 hr and subsequently tested for reactivity. Cells from the same thymectomized donor mice exposed in parallel to extracts from syngeneic spleen or mesenteric lymph node at an equivalent protein concentration did not initiate a graft-versus-host response.
These experiments demonstrate that immune reactivity in the graft-versus-host response involves activation of lymphoid cells by a humoral factor of the thymus acting directly upon these cells.
The cell-mediated immune response of animals to a lethal syngeneic tumor was investigated by inoculating C57BL mice with Lewis lung carcinoma (3LL) cells. T lymphocytes, obtained from the enlarged spleens of the tumor-bearing mice were found t o be cytotoxic t o 3LL target cells in vitro. However, we found that such spleen cells enhanced tumor growth in v i v o when mice were injected with a mixture of spleen cells and tumor cells. Removal of T lymphocytes by treatment of the spleen cells with anti-@ serum plus complement reduced the enhancement of tumor growth. Hence, the tumor enhancing cells, like the cytotoxic cells, appeared t o be T lymphocytes. Removal of T lymphocytes from normal mice by adult thymectomy before tumor inoculation led t o a reduction in the number of tumor metastases. Thus, enhancing T lymphocytes appear t o exist in normal as well as in tumor-bearing mice. Investigation of this mechanism of tumor enhancement suggested that the enhancing T lymphocytes act as suppressor T cells inhibiting natural immune resistance t o tumor growth.
The immuno‐reactivity of C57BL mouse spleen cells previously sensitized in vitro against syngeneic fibroblasts or syngeneic 3LL Lewis tumor cells was investigated. The sensitized spleen cells were assayed in vitro to test their cytotoxicity against the 3LL tumor cells. In addition, spleen cells autosensitized against syngeneic fibroblasts were mixed with 3LL tumor cells and injected into syngeneic recipient mice in order to ascertain their influence on tumor growth. The in vitro assay indicated that lymphoid cells specifically sensitized against either fibroblasts or tumor cells were equally cytotoxic against the 3LL target cells. On the other hand, in the in vivo experiments lymphoid cells sensitized against syngeneic fibroblasts promoted the growth of the 3LL tumor. An attempt to explain the underlying mechanisms involved in the paradoxical behavior of autosensitized lymphocytes is reported herein.
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