Transplantable polyomavirus-induced salivary gland epitheliomas are populated by immature T cells derived from the host.

Transplantable, polyomavirus-induced salivary gland epitheliomas were passaged through F1-hybrid mice of C3H/Bittner with BALB/cJ or AKR/J strains and congenic nu/nu athymic mice on the BALB/c background. By analysis of the Thy-1 and Ly-2 (CD8a) alloantigens of the T cells that infiltrated the transplanted tumors, it has been determined that the lymphocytes were derived from the host and not the donor of the epithelial tumor. It is known that the tumor masses in the F1-hybrid and athymic mice were not the result of a secondary tumor induction or transformation of host tissue because the epithelioma could be transplanted back into the strain of origin, C3H/Bittner. Intratumor lymphocytes resembled thymocytes on the basis of their intense staining by anti-Thy-1 reagents, the presence of large fractions of cells that bore both CD4 and CD8a, and the cell-size distribution of the phenotypes. Nu/nu mice carrying epitheliomas infiltrated with host-origin T lymphocytes were not immunologically reconstituted, as judged by the lack of T cells in the spleens of such tumor hosts. The epithelial tumors acted as sites of host T-lymphocyte maturation, but the process was incomplete, and mature T cells did not emigrate to the periphery.

Diverse classes of T-cell lymphomas arise in T-lymphocyte-inductive epitheliomas of the mouse salivary gland.

During the course of serial transplantations of polyomavirus-induced C3H-Bittner salivary gland epitheliomas in F1-hybrid mice, three tumor sublines were found which gave rise to T-cell lymphomas of host origin. The lymphomas resembled spontaneous AKR/J thymic lymphomas in their expression of lymphoid differentiation antigens, and they may represent sequential stages in the differentiation of immature T lymphocytes. We found no evidence that polyomavirus directly induced the lymphomas, rather, the lymphomagenic events paralleled those which occur in spontaneous AKR/J thymic lymphomas.

Histology of transplantable murine epithelial tumors infiltrated with immature T lymphocytes: neoplastic analogues of the thymus.

Serially transplantable murine thymic and salivary gland epithelial tumors were studied by immunohistologic methods and by electron microscopy. At the ultrastructural level, tumors appear to be identical. The large polygonal epithelial cells lack rough endoplasmic reticulum, Golgi apparatus, and secretory vesicles, and are anchored together by tonofilaments and desmosome junctions. Some areas in the tumors are composed solely of the neoplastic epithelium, while other areas are richly "infiltrated" with lymphocytes having a cortical thymocyte phenotype and supported by a lacy dendritic network of neoplastic epithelial cells. Immunohistochemical staining demonstrates that the epithelial cells express class I and class II major histocompatibility gene complex (MHC) antigens, epidermal keratin, and the ER-TR4 and ER-TR5 thymic epithelial markers. Lymphocyte-rich regions show homogeneous staining for both L3T4 (CD4) and Lyt-2(CD8) T-cell antigens.

Transplantable polyoma virus-induced epitheliomas harbor immature T lymphocytes.

Some salivary epitheliomas induced in C3H/Bittner (C3H/Bi) mice by neonatal injection of the fifth in vitro passage of parotid tumor agent isolate of mouse polyoma virus are infiltrated with T lymphocytes having an immature phenotype. Serially transplantable tumor lines have been obtained from primary salivary epitheliomas, and some of these secondary tumors are also infiltrated with variable proportions of immature T cells. A subline has been selected which, in syngeneic hosts, becomes richly infiltrated by immature lymphocytes, as defined by bearing both CD4 and CD8 surface markers. While some sublines produced this infiltrate, others did not. There is no relationship between the extent or nature of the T-cell infiltrate and the passage number (generation) of the tumors or the residence period of the transplanted tumors in the host. The results strongly suggest that subsets of salivary epitheliomas resemble the thymic microenvironment sufficiently that T-lymphocyte maturation, at least in part, proceeds readily.