We propose to continue our studies of the biology of the T cell lymphoma in AKR mice. The overall aim is to develop a better understanding of the viral and cellular interactions which take place in this mouse strain to produce thymic lymphoma. The program is built on past observations from this and other laboratories and proposes three innovative approaches. First, we have demonstrated prelymphoma cells in the bone marrow. These cells are not capable of autonomous growth but they become lymphoma cells after they migrate to the thymus. We will study the phenotype of these cells. Attempts will be made to grow them in vitro. It will be determined if in vitro infection with cloned AKR lymphomagenic viruses can result in the expression of prelymphoma cells. A second part of this proposal will be to study the in vivo spread of lyphomagenic viruses in the tissues of 'virus free' strains of mice (CBA/H and NFS). Certain cloned isolates of the AKR viruses which are lymphoma-accelerating for the AKR strain induce thymic lymphoma in these two strains while others do not, thus, making a comparison of the organ (tissue) expression of these viruses of interest. In the third part of the proposal, we will study lymphoma cell lines for their sensitivity or resistance to corticosteroids. Steroid sensitive and resistant clones have been isolated from a parent AKR lymphoma cell line. The resistant cell line containing normal numbers of hormone receptors appears to result from an in vitro differentiation of the hormone sensitive cells. We wish to determine if resistant cells lines can be derived after in vivo inoculation of the sensitive lines and to study the in vivo growth properties of these lines. These two cell lines will also be used for a new experimental approach to molecularly clone the genes for steroid induced lysis which vary in their expression at different stages of T cell differentiation.
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