quences. Mol Cell Biol 12:2396-2405. 
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4415-4422. 
MOLECULAR ASPECTS OF DIFFERENTIATION AND PROLIFERATION 
OF THE LYMPHOID SYSTEM 
Craig B. Thompson, M.D., Associate Investigator 
Dr. Thompson and his colleagues are focusing on 
the characterization of molecular events associated 
v^^ith cellular differentiation and proliferation of the 
immune system. At present the laboratory is mainly 
engaged in investigating 1) the regulation of gene 
expression during human T cell activation and pro- 
liferation and 2) B cell development in the avian 
bursa of Fabricius. 
Normal Human T Cells as a Model System 
for Study of Gene Expression During 
Cellular Activation 
For a number of years the laboratory has studied 
the expression and function of nuclear oncogenes. 
Since many of the nuclear proto-oncogenes play im- 
portant roles in the regulation of cellular prolifera- 
tion, this work has led to an expanded interest in 
understanding molecular events associated with the 
transition of a cell from a quiescent state to one of 
either cellular proliferation or effector function. To 
study these events in a normal cell population, the 
group has chosen to study molecular events asso- 
ciated with human T cell activation. 
The laboratory has concentrated on how molecu- 
lar events transduced through the T cell receptor 
and accessory T cell surface molecules regulate the 
expression of genes associated with cellular prolifer- 
ation and T cell function. These genes include the 
nuclear proto-oncogenes, lymphokine genes, T cell 
receptor genes, and activational T cell surface re- 
ceptors. Over the past several years, the group has 
been concentrating on the expression and function 
of the Ets family of proto-oncogenes, and has been 
able to demonstrate that these genes are reciprocally 
expressed during T cell activation. Ets-\ is selec- 
tively expressed in quiescent cells, while Ets-2 is 
expressed in cells activated through the T cell re- 
ceptor. Recent studies in collaboration with Dr. 
Jeffrey Leiden (HHMI, University of Michigan) have 
demonstrated that Ets-l plays a major role in the 
transcriptional regulation of T cell quiescence. In 
contrast, Ets-2 may play a role in the transcriptional 
induction of T cell activation genes required for cell 
proliferation. 
In addition. Dr. Thompson's group has now iden- 
tified several additional Ets-vclztcd genes that are 
differentially expressed during T cell activation. 
One of these genes, Elf-1, appears to play an impor- 
tant role in the regulation of HIV- 2 (human immuno- 
deficiency virus type 2) as well as several T cell 
activation genes. Surprisingly, the Elf-1 protein was 
found to be expressed constitutively in the T ceil 
nucleus. 
To explain how Elf-1 could play a role in activa- 
tional gene expression, the group has been examin- 
ing the molecular interactions of Elf-1 with other 
nuclear regulatory proteins. In resting T cells, Elf-1 
appears to bind specifically to the retinoblastoma 
protein Rb. As T cells undergo activation and cell 
cycle progression, Rb is phosphorylated, and phos- 
phorylated Rb does not bind to Elf- 1 . Thus Elf- 1 is a 
transcription factor that directly interacts with a 
protein involved in cell cycle regulation. Studies are 
under way to elucidate how these interactions regu- 
late Elf-1 transcriptional events. 
The laboratory has also continued to characterize 
a novel T cell activation pathway that is both de- 
fined and regulated by the CD28 surface molecule. 
The CD28 pathway coordinately regulates the ex- 
pression of lymphokine genes in antigen-activated T 
cells. Lymphokine production is one of the major 
effector functions of T cells and serves to regulate 
the responses of many of the other types of inflam- 
matory cells. Several new aspects of signal transduc- 
tion through CD28 have been defined. 
CD28 activation involves specific induction of a 
IMMUNOLOGY 
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