Helper T cells, also known as CD4+ T cells, are a type of white blood cell that coordinates the immune system's response. They produce cytokine signaling molecules that recruit other immune cells and direct the type of response. There are several subsets of helper T cells that each secrete a specific profile of cytokines in response to different pathogens, including Th1, Th2, Th17, Treg, Tfh, and Th22 cells. The differentiation of each subset is controlled by a network of transcription factors that turn on genes for the subset's unique functions in fighting infection or regulating immune responses.

1. Helper T Cells-
The ‘quarterback’ of Immune System
By-
Arindam Sain, CSIR- JRF, M.Sc.(Physiology)
PHYSIOLOGY NEWS

2. Helper T Cells- An Introduction
 Helper T cells can produce many different cytokines – protein
molecules which they use to communicate with the rest of the
immune system
 As the “quarterback” of the immune system team, the helper T cell
uses cytokines to “call the plays”
 These include cytokines such as TNF, IFN-γ, IL-4, IL-5, IL-6, IL-10, IL-
17, and IL-21
 A single Th cell doesn’t secrete all these different cytokines
 Th cells tend to secrete subsets of cytokines– subsets which are
appropriate to orchestrate an immune defence against particular
invaders
 So far, three major subsets have been identified: Th1 , Th2 , and Th17

3. The CD4+ T cell differentiation
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4. A Network of Transcription Factors Determines Th1/Th2
TH1:
• T-bet is regarded as the master regulator for Th1 cell differentiation and
IFN-γ production
• T-bet is not expressed in naive CD4+ T cells, but is readily induced in
response to TCR, IFN-γ and IL-12R signalling pathways
• Selective expression of T-bet accounts for TH1 cell development and for
the TH1 cell-specific expression of IFNγ
TH2:
• The role of GATA3 in Th2 cells is well known as the master regulator to
guide the differentiation of Th2
• The expression of GATA3 is induced by the TH2-cell-inducing cytokine
interleukin-4 (IL-4) in a signal transducer and activator of transcription 6
(STAT6)-dependent manner
Other important transcription factors in Th1/Th2 lineages are RUNX family,
IRF4, DEC2, STAT family etc.

5. The network of transcription factors in Th1/2 cells
Y. Zhang et al. PHYSIOLOGY NEWS

6. Th1/2 cells differentiation and their micro-/lnRNA signatures
Y. Zhang et al.

7. M. Piccioni et al.
The signalling pathways involved in Treg cell development
• Regulatory T-cells (Treg)
represent a subset of CD4+ T-
cells characterized by high
suppressive capacity, which
can be generated in the thymus
or induced in the periphery.
• Tregs suppress activation,
proliferation and cytokine
production of CD4+ T cells and
CD8+ T cells
• Tregs can produce soluble
messengers which have a
suppressive function, including
TGF-beta, IL-10 and adenosine
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8. Regulatory T cell Properties
ThermoFisherScientific PHYSIOLOGY NEWS

9. The differentiation of Th17 cells
• CD4+ T helper cells are
classical but constantly
reinterpreted T-cell subset,
playing critical roles in a
diverse range of inflammatory
responses or diseases
• CD4+ T helper cells are
classical but constantly
reinterpreted T-cell subset,
playing critical roles in a
diverse range of inflammatory
responses or diseases.
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10. The regulation of Th17 cell differentiation
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11. • Follicular helper T cells (Tfh) are a newly defined helper T-cell subset
that is specialized in facilitating B-cell responses.
• These cells have a unique tissue localization pattern and a distinct
transcriptional program suited for the B-cell helper function
H. Qi et al.

12. L. Jia and C. Wu
• Interleukin-9 (IL-9) has been
shown to have various effects
on different cell types
• Activates mast cells to secrete
several products, including IL-
13, which exerts its effects on
the epithelial cells of the lung
and gut
• IL-9 seems to have a direct
effect on regulatory T (Treg)
cells, T helper 17 (Th17) cells,
and antigen presenting cells
(APCs). TGF-β, transforming
growth factor-β
Differentiation and Targets of IL-9 function

13. • Th22 cells play a critical role in
the late-stage of intestinal
pathogen immunity
• IL-6-mediated differentiation
and/or accumulation of Th22
cells and their production of IL-
22 dominate the elimination of
the pathogen in the later stage
• IL-23 can induce IL-6
production by antigen-
presenting cells, which then
further contributes to the
induction of Th22 cells
• TGF-β can induce the
development of Th17 cells and
suppress the generation of
Th22 cells
Role of Th22 in Immunity
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14. IL-22-IL-22R1 signalling pathway
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15. THANK YOU
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