Characterization of preneoplastic thymocytes and of their neoplastic progression in irradiated C57BL/Ka mice
- Stanford Univ. School of Medicine, CA (United States)
Mice that receive whole body split-dose irradiation develop thymic lymphomas after a long latent period. Before emergence of frank lymphomas, preneoplastic thymocytes, which are defined by their ability to progress to full malignancy on intrathymic transfer to congenic hosts, appear. A combination of mAb 1C11, which binds to a cell surface glycoprotein on lymphoma cells, and of Abs to the differentiation markers CD4 and CD8 (MHC co-receptors), and CD3 (TCR complex) was used to characterize the phenotypes of preneoplastic thymocytes and to place them within the scheme of normal T cell ontogeny. In the irradiated, preneoplastic thymus, the 1C11 molecule was found to be present on CD4{sup {minus}}8{sup {minus}}, CD4{sup {minus}}8{sup +}, and CD4{sup +}8{sup +}, but not CD4{sup +}8{sup {minus}}, cells. After intrathymic transfer to Thy-1 congenic recipients, 1C11{sup high}CD4{sup {minus}}8{sup {minus}} cells from irradiated mice showed the highest leukemogenic potential, followed by the 1C11{sup high}CD4{sup {minus}}8{sup +} and 1C11{sup high}CD4{sup +}8{sup +} subsets. Within the 1C11{sup high}CD4{sup {minus}}8{sup {minus}} subset, CD3{sup +} cells were more leukemogenic than CD3{sup {minus}} cells. The resulting lymphomas were 1C11{sup high}CD3{sup +}4{sup +}8{sup +}, phenotypes that are absent or very rare in the normal thymus, but similar to those of primary radiation-induced lymphomas. Examination of the TCR V{beta} repertoire in these lymphomas shows a highly significant bias, in that approximately 50% express the V{beta}8 gene product. These results indicate, but do not prove, that the 1C11{sup high}CD3{sup +}4{sup {minus}}8{sup {minus}} cells, a very small subset of normal thymocytes, are either the target of neoplastic transformation after radiation or the earliest identifiable cell population after the transforming event. These results also suggest at least one possible pathway to define the processes leading to overt lymphoma. 51 refs., 7 figs., 3 tabs.
- OSTI ID:
- 86503
- Journal Information:
- Journal of Immunology, Vol. 153, Issue 4; Other Information: PBD: 15 Aug 1994
- Country of Publication:
- United States
- Language:
- English
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