Roza I. Nurieva & Chen
Dong talk with ScienceWatch.com and answer a few
questions about this month's Fast Moving Front in the field
of Immunology.
Article: Generation of T follicular helper cells is
mediated by interleukin-21 but independent of T helper 1,
2, or 17 cell lineages
Authors: Nurieva,
RI;Chung, Y;Hwang, D;Yang, XO;Kang, HS;Ma, L;Wang,
YH;Watowich, SS;Jetten, AM;Tian,
Q;Dong,
C
Journal: IMMUNITY, 29 (1): 138-149 JUL 18 2008
Addresses: Univ Texas MD Anderson Canc Ctr, Dept Immunol,
Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX
77030 USA.
Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci,
Houston, TX 77030 USA.
Pohang Univ Sci & Technol, Dept Chem Engn, Kyungbuk
790784, South Korea.
(addresses have been truncated)
Why do you think your paper is highly
cited?
Upon activation, CD4+ T cells differentiate into distinct effector lineages
that regulate different types of immune responses. Germinal center
structures where activated B cells undergo tremendous proliferation have
been associated with autoimmune diseases and B cell lymphomas.
Follicular helper T (Tfh) cells have been recently found to be localized in
germinal centers and are specialized in providing help for B cells.
Although Tfh cells are important in humoral immunity, their developmental
regulation has been unclear.
In this article, we extensively characterized the developmental regulation
of Tfh cells. We demonstrated that Tfh cells are distinct in their gene
expression and immune function and develop via a pathway that is dependent
on IL-21 or IL-6 but independent of T helper (Th)1, Th2, or Th17 lineages.
Thus, this study significantly advances our understanding of the biology of
Tfh cells.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
Coauthor
Chen Dong
Yes, it describes for the first time the developmental regulation of Tfh
cells. In addition, we developed a method to generate Tfh cells in
vitro.
Would you summarize the significance of your paper
in layman's terms?
This paper provides the evidence that defines Tfh cells as a distinct
T-cell subset, and shows that interleukin-21 plays a critical role in their
differentiation. This knowledge may help us to find ways to treat
antibody-mediated autoimmune diseases and B lymphoma.
How did you become involved in this research, and
were there any problems along the way?
Our previous work has indicated an important role of inducible
costimulatory receptor (ICOS) and its ligand, B7h, in regulation of humoral
immunity, especially germinal center reactions.
We also studied the role of IL-21 in Th17 cell differentiation. Since Tfh
cells are regulated by ICOS and they also express IL-21, we decided to
carry out an extensive analysis of Tfh cell development and their
relationships with other types of T cells, especially Th17 cells.
To determine the factors involved in Tfh cell development, we utilized many
gene knockout animals, including those provided by Dr. Anton M. Jetten's
group in the National Institute of Environmental Health Sciences
(NIEHS) at the National Institutes of Health (NIH).
Where do you see your research leading in the
future?
Although our paper described Tfh cells as a distinct lineage of T cells, it
did not provide any genetic mechanism whereby Tfh cell development is
programmed, especially by lineage-specific transcription factor.
In August, our group and several others published reports that illustrate
Bcl6 as a transcription factor that is selectively expressed by Tfh cells
and is necessary for Tfh cell development and germinal center reactions.
These studies support our ideas that Tfh cells represent a unique subset of
T cells. At the moment, we do not know very much about mechanistically how
Bcl6 works. In addition, we would like to address the stability and
plasticity of Tfh cell genetic program.
Do you foresee any social or political implications
for your research?
Yes. Antibody-producing B cells need to be tightly controlled. Any
dysregulation of T-cell function can have a significant effect on the
antibody-producing B cells. For example, excessive function of Tfh cells
has been attributed to the pathogenesis of antibody-mediated autoimmune
diseases such as lupus.
B lymphomas often arise from germinal centers. In this regard, specific
targeting of the Tfh pathway will help to prevent or treat these diseases.
Roza I. Nurieva, PhD.
Assistant Professor
Department of Immunology
MD Anderson Cancer Center
Houston, TX, USA Web
Chen Dong, Ph.D.
Professor
Department of Immunology
MD Anderson Cancer Center
Houston, TX, USA Web