PMC

Tumor development in crosses of susceptible FVB.TCRδ^2/2 with resistant C57BL/6.TCRδ^2/2 mice. FVB.TCRδ^−/− (FVB.δ^−/−) and C57BL/6.TCRδ^−/− (B6.δ^−/−) mice were bred to produce F₁.δ^−/−, F₂.δ^−/−, and (F₁ × FVB) backcross (BC).δ^−/− offspring. Under a two-stage chemical carcinogenesis protocol of initiation with 200 nmol DMBA and weekly application of (low dose) 5 nmol TPA, mice were followed for the development of all cutaneous tumors (papillomas or carcinomas >1 mm) at week 16 after DMBA initiation. The mean number ± standard deviation of total tumors per animal for each group is represented. Although none of the B6.δ^−/− mice developed more than two tumors, 46.3% of the BC.δ^−/− and 26.2% of the F2.δ^2/2 mice developed more than two tumors.

Rapid tumor onset and increased tumor incidence in TCRδ^−/− and TCRβ^2/2δ^2/2 mice. Under a two-stage chemical carcinogenesis protocol of initiation with 200 nmol DMBA and weekly application of (low dose) 5 nmol TPA, WT (w.t.) and T cell–deficient mice were followed for the development of all cutaneous tumors (papillomas or carcinomas >1 mm; see and for breakdown). Although TCRβ^−/− mice (deficient in only αβ T cells) showed no significant difference in tumorigenesis relative to WT mice, TCRδ^−/− mice (deficient in γδ T cells) and TCRβ^−/−δ^−/− mice (deficient in both αβ and γδ T cells) exhibited an earlier onset and marked increase in tumor development. *, P ≤ 0.0001 for β^−/−δ^−/− and δ^−/− versus WT or β^−/−.

Marked decrease in tumor burden and progression in TCRβ^−/− mice. Under a two-stage chemical carcinogenesis protocol of initiation with 200 nmol DMBA and weekly application of (high dose) 40 nmol TPA, WT (w.t.) and TCRβ^−/− mice were followed for the development of tumors (>1 mm). TCRβ^−/− mice deficient in αβ T cells demonstrated a markedly lower (A) tumor area and (B) carcinoma development. (C) Clinical tumor appearance of two representative mice from each of the WT and β^−/− groups. (D) Representative flow cytometric analysis for the presence of αβ⁺ (H57) T cells in the spleens of 6-wk-old TCRβ^−/− mice, WT mice, and TCRβ^−/− mice reconstituted at birth by intraperitoneal injection of day 13.5 FLHSCs. (E and F) Reconstituted TCRβ^−/− mice (β^−/− + αβ T cells) demonstrated a higher tumor area (E) and greater rate of carcinoma formation (F) than TCRβ^−/− mice. *, P ≤ 0.02; **, P ≤ 0.01; ***, P ≤ 0.005.

Morphologic assessment of tumor development in T cell–deficient mice. Tumors that developed under two-stage chemical carcinogenesis (refer to ) were scored as clinically apparent papillomas (P) or carcinomas (C), as described in Materials and Methods. (A) Hematoxylin and eosin–stained sections of representative tumors were obtained and typical examples are shown. This papilloma (P1; see text for scoring index) exhibited a symmetric outline, acanthosis, and papillomatosis (×40), with uniform keratinocytes with moderately abundant cytoplasm and small round nuclei (×100). This early carcinoma (C2) exhibited an asymmetric outline and expansion of neoplastic follicle-like structures composed of atypical epithelium (×40). There was haphazard infiltration of the dermis by pleomorphic keratinocytes with increased nuclear/cytoplasmic ratio (×100). This later stage carcinoma (C3) exhibited a poorly organized, asymmetric pattern of growth (×40) comprised of atypical keratinocytes aggregated around vascular connective tissue cores (×100). (B) Papilloma and carcinoma development for the experiment depicted in at 17 wk. *, P < 0.05; **, P < 0.01; ***, P < 0.005; ****, P < 0.001. (C) Papilloma and carcinoma development in a second independent experiment at study termination. n.d., not done. (D) Tumor appearance of two representative mice from each of the TCRδ^−/− and TCRβ^−/−δ^−/− groups.