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2. Toll-like receptor signalling during infection and inflammation
- Prof. Luke O'Neill
-
3. Cytokines and CD4 T Cells: dance partners at the immunology ball
- Dr. William E. Paul
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4. The gamma c family of cytokines
- Dr. Warren J. Leonard
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5. Interleukin-6: back to the future
- Prof. Tadamitsu Kishimoto
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6. Regulation of the immune response to pathogens 1
- Prof. Anne O’Garra
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7. Regulation of the immune response to pathogens 2
- Prof. Anne O’Garra
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8. IL-17 cytokine family and receptors
- Prof. Chen Dong
- Dr. Seon Hee Chang
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9. The b common (bc) family of cytokines, receptors and ligands
- Prof. Angel Lopez
- Dr. Timothy Hercus
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12. IL-1 as a key inflammatory regulator in autoinflammatory diseases
- Dr. Raphaela Goldbach-Mansky
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13. Signaling for the interferon family of receptors and ligands and clinical implications
- Prof. Leonidas Platanias
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14. Interferons as antivirals: translating basic research into clinical application
- Prof. Eleanor N. Fish
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15. Chemokines and their receptors: their biology and therapeutic relevance
- Dr. Amanda Proudfoot
-
16. Humoral innate immunity and the acute phase response 1
- Prof. Alberto Mantovani
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17. Humoral innate immunity and the acute phase response 2
- Prof. Alberto Mantovani
-
18. Receptor identification for alarmins and DAMPs
- Dr. Joost J. Oppenheim
-
19. Assays for cytokines and cytokine assay performance 1
- Prof. Theresa Whiteside
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20. Assays for cytokines and cytokine assay performance 2
- Prof. Theresa Whiteside
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21. Interleukin-7 and T cells
- Dr. Scott Durum
- Archived Lectures *These may not cover the latest advances in the field
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22. Assays for cytokines and cytokine assay standardization
- Prof. Theresa Whiteside
Printable Handouts
Navigable Slide Index
- Introduction
- Fates and functions of CD4 Th cells
- Genome-wide analysis among CD4 T cells
- Signature cytokine gene accessibility
- Master regulatory transcription factors
- Chromatin accessibility during T cell differentiation
- Plasticity
- Each Th cell has unique GATA3-bound genes
- GATA3 binds to different sites in different T cells
- GATA3 adds repressive marks in Th2 cells
- Binding of Fli-1 to Th2 cytokine locus
- GATA3 regulates gene expression - by cell type
- Transcription factor networks for Th2 differentiation
- GATA3, STAT5 - vital for Th2 cell differentiation
- Proposed model for Th2 differentiation
- TCR signal controls GATA3 and IL-4 transcription
- High peptide concentration suppresses GATA-3
- IL-2 is required for early IL-4 transcription
- IL-2-dependent STAT5 phosphorylation
- Effect of MAPK inhibitors on IL-4 producers
- MEK inhibitor partially restores Phospho-Stat5
- MEK inhibitor relieves suppression of GATA-3
- Expression of IL1R family members on Th cells
- Unique IL-1R expression, reliance on STAT
- IL-18 induces IFNg production in Th1 cells
- Proposal
- IL-1 enhances CD4 T cell responses
- Only IL-1b and IL-1a enhance responses
- IL-1 directly enhances responses in CD4 T cells
- IL-1 action on CD4 T cells to enhance responses
- IL-1 action on CD4 T cells is cell autonomous
- IL-1 principally enhances Th17 responses
- IL-1 'adjuvant' effect
- Thank you
Topics Covered
- Naive CD4 T cells differentiate into various Th effector classes
- Each Th cell type has a specific function in responding to infectious agents
- Differentiated states may be plastic
- Cytokine activated cytokine production
- Epigenetic regulation of Th differentiation
Talk Citation
Paul, W.E. (2012, December 18). Cytokines and CD4 T Cells: dance partners at the immunology ball [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 6, 2024, from https://doi.org/10.69645/KYAB1354.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. William E. Paul has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Immunology
Transcript
Please wait while the transcript is being prepared...
0:00
Let me introduce myself.
My name is William Paul.
I'm a scientist at the Laboratory of Immunology at
the National Institute of Allergy and Infectious Diseases.
My presentation is entitled Cytokines and CD4 T Cells:
Dance Partners at the Immunology Ball.
By this title, I mean to discuss with you
my own views of the critical interactions between the cytokines,
particularly those made by T cells,
and those that influence particularly the differentiation of CD4 T cells.
0:39
Let us begin with a discussion of the fates and functions of CD4 Th cells.
The naïve CD4 T cell is a rather remarkable cell.
It is basically a nucleus with the barest rim of cytoplasm.
Yet within it is the potentiality to achieve a series of distinct
differentiated states that we have known about over the last 20-25 years,
when the distinction between Th1 and Th2 cells was first realized.
We know that Th1 cells have, as their principal function,
the dealing with intracellular pathogens,
and that when they are dysregulated,
they can be responsible for much tissue-specific autoimmunity.
Th2 cells, my personal favorites,
have an important role to play in protection against extracellular parasites,
and when they are dysregulated,
they result in allergic inflammatory disorders.
More recently defined are the Th17 cells.
They are important in providing protection against extracellular bacteria and fungi.
They too, when dysregulated,
cooperate a good deal with Th1 cells in mediating organ-specific autoimmunity.
Finally, the induced or iT regulatory cells,
which together with their congeners,
the natural T regulatory cells,
play a critical role in immune tolerance and lymphocyte homeostasis.
What defines the distinctive functionalities
of these distinctive cell types are two features.
One, the suite of cytokines that they produce,
and secondly, the chemokine receptors that they express.
The former causing their effective functions,
and the latter allowing them to be directed to the sites
where they will mediate their functionality.
Each of the four different cell types mediates or produces a signature cytokine.
For Th1 cells,
that is interferon-gamma (IFN-γ).
For Th2s, again my personal favorite, it is interleukin-4 (IL-4).
For Th17s, it would be IL-17a,
and finally for iTregs it will probably be TGF-β,
although this would still be a matter of some uncertainty.
One of the most attractive features of the study of this set of differentiated cells,
is the fact that we understand with great precision
how to carry out this differentiation in vitro.
This has two very important effects.
One, it allows us to understand, in very considerable detail,
the distinctive molecular events involved in the differentiation process.
Secondly, because the initiating cells can be
obtained in very large numbers and in highly purified form,
and we understand their biology with a great deal of precision,
it presents itself as one of the very best mammalian systems in which we study differentiation.
The process of a naïve CD4 T cell differentiating to the four distinctive types,
firstly involves the engagement of the T cell receptor with its cognate antigen,
and secondly, involves the establishment of a particular cytokine milieu.
In general, two critical cytokines are involved.
For Th1 cells,
that is IFN-γ plus IL-12,
for Th2 cells its IL-4 plus IL-2.
For Th17 cells it is TGF-β plus IL-6 or IL-21.
Finally, for iTreg, it is TGF-β plus IL-2.
One of the very interesting effects that should be noted for Th1,
Th2s and to a lesser degree, Th17 cells,
is that one of the major products of those cells,
Th1's IFN-γ, Th2's IL-4,
is one of the critical inducers.
This is a little more indirect for Th17s in which one generally uses
IL-6 for differentiation purposes, and the cell type produces IL-21,
which can then substitute for IL-6.
But it suggests, as I will discuss later,
the possibility of a very important positive feedback loop in the process of differentiation.
In closing this opening discussion,
I want to point out that we also know the critical transcription factors which underlie
the production of the cytokines that each of
these four cell populations make and that determine the functionalities of these cell.
In each case, there is what is referred to as
a master regulatory transcription factor.
For Th1s that is T-bet,
for Th2s GATA-3,
for TH17s RORγt,
and for induced T regulatory cells Foxp3.
In addition, each of the differentiation processes involve
the use of a cytokine that activates a particular stacked molecule.
Again, for Th1 cells, that is Stat4,
which is of course activated by IL-12,
for Th2 cells it is Stat5 activated by IL-2.
For Th17 cells it is Stat3 activated by IL-6 or IL-21,
and for iTregs, it would be Stat5,
also activated by IL-2.
This gives us a picture of some of
the interesting properties of these very important cell types.
Now, I must also say, that this presentation,
this initial slide, represents somewhat of an oversimplification.
The question of whether the four cell populations I've
described are in fact complete can be discussed in detail.
In fact, almost certainly there are more.
There are the so-called T follicular helper cells,
which are achieving a great deal of prominence.
There are what may be subsets of other populations,
for example, Th9 cells,
which appear to be closely related to Th2 cells,
Th22 cells, which may be closely related to Th17 cells and possibly other cell types.
But the principles that underlie
the differentiation and behavior of these cells, I think,
is well illustrated by our concentration on these particular cell types.
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