CD8+ T cells are crucial for the ability of congenic normal mice to reject highly immunogenic sarcomas induced in nude mice with 3-methylcholanthrene

Abstract

An attempt was made to identify the selection pressures put upon a growing tumour by CD8+ T cells. To this end tumours induced with 3-methylcholanthrene in T cell-deficient nude mice and in congenic T cell-competent nu/+ mice were transplanted to nu/+ recipients. The rejection rate of the sarcomas from nude mice was almost twice that of the sarcomas from nu/+ mice. Depletion of CD8+ T cells from nu/+ recipients prior to transplantation made them accept nude tumours that were consistently rejected by untreated nu/+ recipients. These findings suggest that a methylcholanthrene sarcoma during its growth in a T cell-competent host adapts to the T cell system through a selective elimination of highly immunogenic tumour cells that are susceptible to CD8+ T cell-mediated lysis.

Fig. 1

Acceptance or rejection of transplanted nu/+ and nude tumours by nu/+ recipients. Each tumour was transplanted to 10 normal recipients in the doses 10⁷ (•), 10⁶ (○), or 10⁵ tumour cells (▾). Tumour acceptance for each of the cell doses in the nu/+ recipients is indicated by a solid line with a symbol. The abscissa shows the time in weeks and the ordinate indicates the number of mice accepting the tumour.

Fig. 2

Flow cytometry profile of the cell population in the spleen of a normal immunocompetent nu/+ control mouse receiving rat IgG (a) and a CD8⁺ T cell-depleted nu/+ mouse after 4 weeks of antibody treatment (b). The cells were stained with PE-conjugated anti-CD8b (Lyt 3.2) antibody. The abscissa indicates the fluorescence in arbitrary units and the ordinate the number of cells stained. Fluorescence between 10⁰ and 10¹ is the background staining. Fluorescence in the interval between 10² and 10³ indicates the population of CD8⁺ T cells.

Fig. 3

The outcome of transplantation of three highly immunogenic tumours to CD8⁺ T cell-depleted recipients. Fifteen normal nu/+ mice were depleted with ascites diluted 1:10 approx. 1–2 mg/ml antibody and 15 were depleted with ascites diluted 1:50 approx. 0·2–0·4 mg/ml antibody for each of the three cell lines. Ten nu/+ control mice received rat IgG 1 mg/ml and 10 were given rat IgG 0·2 mg/ml. The abscissa indicates the time measured in weeks and the ordinate indicates the number of mice with tumour acceptance.