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From
•>>July 2006
 Juan
Carlos Zúñiga-Pflücker, PhD
answers a
few questions about this month's fast
moving front in
the field of Immunology. The
author has also
sent along images of their work.
Field: Immunology
Article: Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in
vitro
Authors: Schmitt, TM;Zuniga-Pflucker,
JC
Journal: IMMUNITY, 17 (6): 749-756, DEC 2002
Addresses:
Univ Toronto, Sunnybrook & Womens Coll Hlth Sci Ctr, Dept Immunol, 2075 Bayview Ave, Toronto, ON M4N 3M5,
Canada.
Univ Toronto, Sunnybrook & Womens Coll Hlth Sci Ctr, Dept Immunol, Toronto, ON M4N 3M5, Canada.
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Why do you think your
paper is highly cited?
The main reason is that this paper established a simple and
effective way to study T cell development and to generate
T-lineage cells in the lab. This approach has been quickly adopted
by many labs around the world, since it facilitates the
determination of T lymphocyte lineage potential and direct
examination of how T cells develop.
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“Our paper identified the molecular players that are involved in the creation of an important type of blood-borne immune cells, T cells.”
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This paper also clarified the role of Notch ligands, in
particular, Delta-like as a critical player for the induction of
T-lineage commitment and differentiation. This paper further
established the importance of this pathway, Notch/Delta-like,
which normally takes place within the thymus, the organ where T
cells are generated from stem cells that originate in the bone
marrow.
Does it describe a new discovery, methodology, or synthesis
of knowledge?
This paper provided both a discovery as to the role of
Delta-like in supporting full T cell differentiation, and also
provided a new methodology with which to generate T cells in
vitro from defined sources of stem cells, using a simple
coculture approach.
Could you summarize the significance of your paper in
layman's terms?
Our paper identified the molecular players that are involved in
the creation of an important type of blood-borne immune cells, T
cells. Additionally, this paper allowed us to easily generate T
cells in the lab from many sources of stem cells, which may
benefit immune-deficient individuals, or enable the creation of
designer T cells to fight infections or cancer.
How did you become involved in this research, and were there
obstacles along the way?
My lab has been studying the process of T cell development for
many years, and we became interested in the Notch system following
the publication of two key papers, by the Pear and MacDonald labs.
Prior to that, we had been studying the development of lymphocytes
in culture, and felt that the reason that we could generate
multiple immune cell types but not T cells may have been due to a
lack of the appropriate signals, in this case Notch signals. Our Immunity
paper demonstrated that this was indeed the case. The main
obstacle was to come up with just the right conditions to
effectively induce T cell differentiation.
Are there any social or political implications for your
research?
The main social implication will come from any future
treatments for immunodeficiencies or cancer that may be derived
from the use of the system we described in that paper.
Juan Carlos Zúñiga-Pflücker, PhD
Professor
Department of Immunology
Canada Research Chair in Developmental Immunology
University of Toronto
Toronto, Ontario
And
Senior Scientist
Sunnybrook Research Institute
Toronto, Ontario
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A Closer Look...
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Below
are images sent in by Juan Carlos
Zúñiga-Pflücker which correspond with the featured
paper, or current research. |
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Figure 1:
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Figure
1: A schematic overview of stem cell/OP9-DL1 cell cocultures, and potential applications/experimental approaches of this model system. Stem cells are seeded onto OP9-DL1 cell monolayers, and are induced to differentiate in the presence of cytokines, which support early lymphopoiesis. The length of the culture period depends on the application to be used, and the desired stage of T cell differentiation to be examined. |
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