1. T follicular helper cells (Tfh) are a subset of CD4+ T cells that are specialized to regulate antibody responses and are critical for B cell maturation, antibody class switching, and germinal center formation. 2. Tfh cells differentiate from naive CD4+ T cells upon antigen stimulation by dendritic cells and B cells. Their differentiation is regulated by transcription factors like Bcl-6 and surface markers such as CXCR5, ICOS, and PD-1. 3. Tfh cells function to help B cells by forming germinal centers, selectively stimulating B cells, and producing cytokines that determine antibody type, contributing to humoral immunity.

1. Course Title: General Biomedical Science (TRID631)
Presentation Title: Role of T follicular helper cells
By Aberaw Akalu
February, 2020
Addis Ababa University Graduate Studies
Aklilu Lemma Institute Of Pathobiology

2. Outline of Presentation
» List of abbreviations
» Introduction of Tfh cells
» Differentiation of Tfh cells
» Function of Tfh cells
» Tfh cells and diseases

3. LIST OF ABREVATIONS
 TFH T-follicular cells
 GCs germinal centers
 Bcl-6 B-cell lymphoma 6
 CXCR5 chemokine receptor type 5 (protein encoded by the CXCR5 gene)
 CCR7 chemokine receptor type 7 (protein encoded by the CCR7 gene)
 CXCL13 chemokine ligand 13 (protein encoded by the CXCL13 gene)
 ICOS Inducible Costimulator
 ICOS-L Inducible Costimulator Ligand
 PD-1 programmed cell death-1
 IL-2 Interleukin-2 (is a protein coding gene)
 IL-4 Interleukin-4 (is a protein coding gene)
 IL-6 Interleukin-6 (is a protein coding gene)
 IL-6R Interleukin-6 receptor (is a protein coding gene)
 IL-21 Interleukin-21 (is a protein coding gene)
 MHC II Major Histocompatibility Molecules
 APC Antigen presenting cells

4. Role of T follicular cells

5. 1. Introduction
According to Maogen et al., 2012:Cellular & Molecular Immunology
volume 9;
 Tfh cells help is critical for;
 Activation of B cells maturation
 Antibody class switching
 Germinal center formation; are sites within SLOs: lymph
nodes and spleen where mature B cells; proliferate,
differentiate, and mutate their antibody genes during a normal
immune response to an infection.

6.  In order to lymph nodes contain lymphocytes, a type of white
blood cell, which includes;
 B cells and
 T cells
 B-cells mature in the bone marrow,
 T-cells travel through the bloodstream to the thymus gland and
mature there.

7. Fig 1: T follicular helper cells |British society for immunology| immunology.org

8.  The Tfh cells are a subset of CD4+ T cells (Provide
essential activation signals to B Cells, CD8+ T cells, a
phagocytes) specialized to regulate antibody responses.
• Th 1 (IL-2,IL-12,IL-18,IL-27)
• Th 2 (IL-2,IL-4,IL-25,IL-31)
• Th17 (IL-4,IL-12,TGF-β)
• Th 9 (IL-1,IL-6,IL-21,IL-23,TGF-β)
• Tfh (IL-6,IL-21,CXCL-13)
• Treg (IL-2,Retinoic Acid, TGF-β)
Activated CD4+ T cells
Fig 2: www.creative-diagnostics.com/CD creative diagnostics

9. Introduction…………….cont’d
 The production of Tfh cells are associated with the
 Dendritic cells (DCs) and
 B cells.
 Tfh cells help B cells form germinal centers (GC) differentiate
into
 memory cells and
 plasma cells (antibody-secreting cells) as humoral
responses

10. 2. Differentiation of Tfh cells
(Sadegh et al., 2016: Biomedicine & Pharmacotherapy volume 84);
 Tfh cells have the ability to migrate into;
 Secondary lymphoid tissues in B-cell follicles, and
 Expand germinal centers (GC) that have a close interaction
with B cells.
 Molecular factors that participated in differentiation of Tfh cells
such as;
 Transcription factors,
 Surface receptors and
 Cytokine productions

11. Differentiation of Tfh cells………..cont’d
(Sadegh et al., 2016: Biomedicine & Pharmacotherapy volume 84);
After antigen stimulation,
o Naïve B cells first migrate to T-cell zone, and
o Become activated to form GC with the antigen signal
presented by;
 antigen-presenting cell and
 other costimulatory signals from Tfh cells

12. Differentiation of Tfh cells………..cont’d
(Sadegh et al., 2016: Biomedicine & Pharmacotherapy volume 84);
 Tfh cells can be identified by unique expression of surface
markers (table 2)
 CXCR5 which is attracted toward CXCL-13 presented in
the B cell zone
 CCR7
 ICOS and PD-1
 Cytokines (IL-6, IL-21) and,
 The development and differentiation of Tfh cells has been
regulated by transcription factors, such as B-cell lymphoma 6
protein (Bcl-6)

13. Differentiation of Tfh cells………..cont’d
(Sadegh et al., 2016: Biomedicine & Pharmacotherapy volume 84);
Tfh differentiation is a multi-step process:
 Beginning in the T cell zone of SLOs during an
ongoing immune response
 Differentiation of SLOs are including the tonsil
spleen & lymphoid organs
.

14. Differentiation of Tfh cells………..cont’d
Firstly, Naïve CD4+ T cells recognize via
Their TCR,
Protein peptides presented on MHC Class II
molecules by dendritic cells (DCs)
Additional stimulation via the co-stimulatory
molecule, ICOS-L and
IL-6 cytokine production by DCs provides signals
to the CD4+ T cell to express Bcl-6

15. Differentiation of Tfh cells………..cont’d
At the T and B cell zone border (Fig 2);
 TCR and ICOS-L co-stimulation is handed over
to activated B cells
 allowing developing Tfh to express higher levels of
o CXCR5,
o ICOS and
o PD1 and move to the B cell zone
Eventually,
 Tfh help form GCs and fully differentiated Tfh
within the GC are known as GC Tfh and
 Express the highest level of CXCR5, PD1 and ICOS
 Allowing the cells to migrate towards the B cell zone
(Source: British society for immunology)

16. Fig 3: T follicular helper cells |British society for immunology| immunology.org

17. 3. Function of Tfh (Source: British society for immunology)
 Helping B cells produce antibody against foreign pathogens
 Are essential for germinal center (GC) formation
 Selectively stimulate B cells for GC responses,
 Contributing to Ig production and memory B cell and long-
lived plasma cell development.
 Generation of humoral immunity via their expression of
many molecules factors

18.  B cells within GCs rapid proliferation and allowing the production of
antibody, with greater affinity for their targets
 Cytokine production by Tfh is able to determine the type of antibody
produced. The relationship between Tfh and GC B cells is positively
correlated
 In the absence of Tfh, GCs do not form and antibody defects are
observed under typical situations

19. 4. Tfh cells and diseases
Tfh cells have important roles in ( Source: Kemeny, David., 2012,
Crotty, Shane., 2019 and Jeon, et al., 2016)
Protective immunity against infectious diseases
Regulation of intestinal microbiota
Numerous autoimmune diseases
Probably have important roles for allergies
Cancer immunity

20. Tfh cells and diseases (Qin, L & Waseem, T. et al., 2018) ……..cont’d
 Elevated Tfh activity leads to an increase in germinal center:
formation, activation, and production of auto-Abs in autoimmune
diseases
 In immunodeficiencies, a decrease in Tfh cells has been detected with
dysfunctional GC formation, whereas
 In acquired immunodeficiencies (Ineffective-Abs) such as HIV an
increase in Tfh cells serves as viral reservoirs (Fig 4)

21. Tfh cells and diseases (Qin, L & Waseem, T. et al., 2018)……..cont’d
 In Type 2 diabetes regulatory T cells (Tregs) transition to Tfh
cells via GCs leading to the production of pathological Abs
 In allergy, there is an increase in Tfh cell activation and GC
formation causing the production of IgE (Fig 4)
 Tfh cells in cancers is complex and dependent on the types
of tumors (Fig 4) but generally participated in;
 Support & survival growth of leukocyte subsets
 Support leukocyte recruitment to tumor site

22. Figure 4: Qin, et al., 2018. Insights Into the Molecular Mechanisms of T Follicular Helper-Mediated Immunity and Pathology

23. Thank you