cytes have also been produced, using a temperature- 
sensitive sperm-defective mutation. The laboratory 
has shown that the factors binding to the gut activa- 
tor are not present in oocytes; however, the factor 
binding to the conserved site is present in oocyte 
cytoplasm and presumably reflects a maternal con- 
tribution to ges-1 control. The present aims are to 
use this biochemical system to clone the genes for 
the interacting factors, as well as to investigate the 
behavior of the factors in extracts made from mutant 
worms in which development has been perturbed. 
Dr. McGhee and his colleagues are also investigat- 
ing early development in the much larger and more 
slowly developing parasitic nematode Ascaris 
suum. As a first step in characterizing the system, 
they have measured the rates of DNA synthesis in 
early cleavage cycles. The Ascaris cell cycles con- 
tain a G2 phase as predominant, unlike the cell cy- 
cles of the rapidly developing C. elegans embryos, 
previously shown to consist only of alternations be- 
tween DNA synthesis and mitosis. The laboratory has 
purified an esterase enzyme from Ascaris intestines 
and has obtained sufficient amino acid sequence in- 
formation to identify it as indeed the ges-1 homo- 
logue. However, unlike the gut-specific ges l ex- 
pression patterns in Caenorhabditis, the Ascaris 
ges- 1 gene appears to be expressed in most if not all 
tissues of the body. The hope is that such compara- 
tive studies of gene expression patterns will provide 
insight into gene control mechanisms and their 
evolution. 
Another direction the laboratory has taken is to 
clone and characterize genes in C. elegans that, 
judging from work in other organisms, are certain to 
be important regulatory molecules. For example, a 
C. elegans homeobox gene, ceh-10, has been 
cloned and sequenced. This gene bears striking simi- 
larity to genes expressed in the central nervous sys- 
tem of mammals. The group has also cloned the C. 
elegans homologue of the Drosopbila gene fork- 
head and of the mammalian liver-specific transcrip- 
tion factor HNF-3- Both these latter genes are spe- 
cific to endoderm, although development differs 
widely in insects and mammals. Thus it will be of 
special interest to see where the C. elegans homo- 
logue of forkhead and HNF-3 is expressed during 
nematode development. The aim of these experi- 
ments is to see how highly conserved transcription 
factors are distributed among embryonic germ 
layers in widely diff^erent animals. It is hoped that 
this will reveal general and deep-seated mechanisms 
of embryonic development and will even shed light 
on the evolutionary origin of multicellular animals. 
Dr. McGhee is Professor in the Department of 
Medical Biochemistry at the University of Cal- 
gary, Alberta, and a Medical Scientist of the Al- 
berta Heritage Foundation for Medical Research. 
Article 
Azzaria, M., and McGhee, J.D. 1992. DNA synthesis 
in the early embryo of the nematode Ascaris 
suum. Dev Biol 152:89-93. 
CYTOKINE REGULATION OF IMMUNE RESPONSES 
Tim Mosmann, Ph.D., International Research Scholar 
The immune system is capable of responding to 
an infectious agent by invoking many different ef- 
fector functions. Only certain mechanisms will be 
efi'ective against a particular pathogen, and so it is 
not surprising that the choice of mechanism is care- 
fully regulated by the immune system. Much of this 
regulation is mediated by cytokines secreted by 
cells of the immune system, particularly T cells. Dr. 
Mosmann found several years ago that different sub- 
sets of T cells secrete different sets of cytokines 
when stimulated with antigen, and several investi- 
gators showed that these cytokine patterns are re- 
sponsible for the unique functions of each subset. 
Two major types of T helper cell, THl and TH2, 
are mainly responsible for inducing cell-mediated 
and antibody responses, respectively. The TH2- 
enhanced production of antibodies is particularly 
useful in combating infections with extracellular 
agents — for example, by neutralizing bacterial and 
viral attachment sites or blocking the action of tox- 
ins. In contrast, the cell-mediated delayed-type hy- 
persensitivity (DTH) response results in the local 
recruitment and activation of effector cells, such as 
macrophages and granulocytes, that can efficiently 
kill cells infected with intracellular pathogens. 
The unique cytokines of THl or TH2 cells are 
major regulators of the functions of these cells. For 
example, TH2 cells evoke allergic responses by the 
secretion of interleukin-4 (IL-4), which induces im- 
munoglobulin E production, and lL-5, which in- 
INTERNATIONAL RESEARCH SCHOLARS 
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