No abstract

Transgenic mice expressing the Pim-1 kinase are predisposed to develop T-cell lymphomas with a long latency period of about 7-9 months. However, the exact functional basis of the oncogenic activity of Pim-1 remains obscure. C57BL/6 mice homozygous for the lpr mutation develop a well-described lymphoproliferative syndrome at about 26-30 weeks of age. This syndrome is characterized mainly by the accumulation of abnormal T cells in lymph nodes because of the lack of Fas receptor-induced apoptosis. We rind that backcross ofE.-Pim-1 transgenics (mice with a transgene that carries the mouse Pim-l gene under the transcriptional control of the immunoglobulin heavy chain gene enhancer EIs) into lpr/lpr mice results in strong acceleration of lymphoproliferation and dramatic enlargement of lymph nodes. In addition, we show here that cultured lymph node cells from E,u-Pim-1 lpr/lpr mice are rescued from rapid apoptosis that normally occurs in nontransgenic lpr cells in vitro. We also present evidence that CD4+/CD8 double-positive thymocytes from lpr/lpr mice are sensitive to dexamethasone-induced apoptosis, although lpr/lpr mice lack the Fas receptor. In contrast, E,u-Pim-1 lpr/lpr animals show considerable protection from dexamethasone-induced apoptosis. These results show that Pim-1 can strongly accelerate lymphoproliferation through inhibition of apoptosis and thereby provide first insight into the functional basis for the oncogenic activity of Pim-l.Mice homozygous for the lpr mutation show enlargement of cervical lymph nodes because of a proliferation of abnormal yet nonmalignant T cells that bear B220 and Thy-1.2 but lack CD4 and CD8 surface markers (for review, see refs. 1 and 2).

No abstract

The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.