Title page for ETD etd-06062008-154644
|Type of Document
||Hassuneh, Mona Rushdi
||Role of autocrine growth factors in the tumorigenic transformation of T cells
|Nagarkatti, Prakash S.
|Schurig, Gerhardt G.
|Tyson, John J.
|Wong, Eric A.
|Date of Defense
In the current study we tested the hypothesis that tumorigenic
transformation of T cells may result from aberrant regulation of autocrine growth
factor production. We describe for the first time characterization of several
normal T cell lines that underwent spontaneous transformation resulting from
constitutive expression of interleukin-2 (IL-2) and interleukin 2 receptor (IL-2R)
genes. Such cell lines could induce tumors in vivo and furthermore, the growth
of such transformed cells both ex vivo and in vivo could be inhibited by
monoclonal antibodies (mAbs) or antisense oligonucleotides specific for IL-2 or
IL-2R. Interestingly, an in vivo originated T cell lymphoma, LSA, was also found
to be dependent on constitutive production of IL-2 and Interleul(in-4 (IL-4).
Together, these data demonstrated that dysregulation in the production or
respnsiveness to autocrine T cell growth factors, plays an important role in T cell
transformation and tumorigenicity. Due to their ability to produce T cell growth
factors, such tumor cells were found to be highly immunogenic. Thus it was
surprising that some T cell lymphomas could still grow in an immunocompetent
host and kill the host. To this effect, we investigated additional mechanisms
used by such tumor cell lines to grow in an immunocompetent host. It was noted
that the tumor cells used mechanisms such as failure to express MHC and
production of immunosuppressive cytokines, such as, transforming growth
factor-β (TGF-β) and interleukin-10 (IL-10), to evade the action of the immune
system. In addition, the T cell lymphomas constitutively expressed F as-ligand
and triggered apoptosis of host T cells that expressed Fas. Together, the
current study suggests that cytokines produced by the tumor cells play an
important role in tumorigenic transformation as vvell as maintenance of tumor
growth in an immunocompetent host.
|| Approximate Download Time
| 28.8 Modem
|| 56K Modem
|| ISDN (64 Kb)
|| ISDN (128 Kb)
|| Higher-speed Access
next to an author's name indicates that all
files or directories associated with their ETD
are accessible from the Virginia Tech campus network only.
If you have questions or technical
problems, please Contact DLA.