Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia...
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Transcript of Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia...
![Page 1: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/1.jpg)
Regulatory T-cells and Autoimmunity
Uma ChandrasekaranGraduate Student,
Medical College of Georgia
Bits Embryo Lecture
![Page 2: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/2.jpg)
Basics
Components of Immune system:
“All cells of Immune system originate in the bone marrow.”
![Page 3: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/3.jpg)
Basics ….
Principles of innate and adaptive immunity
Innate immunity: 1st line of defense - initial recognition of self-nonself. Lack of Immunological memory
Adaptive Immunity: Random generation of Ag receptors Clonal selection – Basic operating principle Hall mark:Specificity & Immunological Memory
![Page 4: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/4.jpg)
Components of Adaptive response
- T-cells & B-cells
3 different types of T-cells:
1) Helper T-cells (Th) :CD4+ T-cells
2) Cytotoxic T-cells (Tc):CD8+T-cells
3) Regulatory T-cells(Tregs):CD4+ CD25+ T-cells
![Page 5: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/5.jpg)
Discovery of Tregs
Whole T cells
CD25– T cell
SCID/Nude mice
Normal
Autoimmune Disease,IBD
* IBD –Inflammatory Bowel disease,SCID-Severe Combined Immunodeficiency mice
Loss of Tregs : Break of Self-Tolerance (Autoimmunity)
![Page 6: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/6.jpg)
Markers of Tregs
Cell Surface markers -CD4 + T cells
- CD 25 + (high)
Intracellular markers
-Foxp3 - CTLA4 (high)TR - Regulatory T-cell
TE - Effector T-cell
APC-Antigen Presenting Cell
![Page 7: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/7.jpg)
CD 25 :T-cell activation marker
CD 25 : IL-2 receptor Chain
So,CD25 is not an exclusive marker of Tregs
![Page 8: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/8.jpg)
Foxp3 : Treg cell lineage Specification factor
IPEX : X-linked immunodeficiency syndrome associated with autoimmune disease in multiple organs (Humans)
*Immune dysregulation.polyendocrinopathy,enteropathy,X-linked syndrome
Foxp3 Mutation
Foxp3, transcription factor expressed specifically in Tregs
Scurfy Mice: Fatal X-linked lymphoproliferative disease similar to IPEX
![Page 9: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/9.jpg)
Functional Characteristics of Tregs
Immunosuppressive – dampen both innate & adaptive immune response
Thus ,function as critical mediators of
self-tolerance and Immune homeostasis.
![Page 10: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/10.jpg)
Potential Clinical applications of Tregs
CD4+ 25 + Treg function
CD4+ 25 + Treg function
Target condition Approach
Organ transplant,Autoimmunity,allergy
Cancer,Infectious disease
Transfer of Tregs
Removal of Tregs/block their function
![Page 11: Regulatory T-cells and Autoimmunity Uma Chandrasekaran Graduate Student, Medical College of Georgia Bits Embryo Lecture.](https://reader036.fdocuments.us/reader036/viewer/2022062517/56649ef75503460f94c0ab44/html5/thumbnails/11.jpg)
Current research focus in Treg Immunology
Expansion /Enrichment of naturally occurring Tregs
- Naturally occurring Tregs constitute only 5-10% of CD4 T cells
- as they are anergic cells, difficult to expand invitro.
Specific markers for Tregs
- CD25+ and Foxp3 are also expressed on activated cells
Understanding the mechanism of immunosuppression
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References
1. Sakaguchi S. J.Exp.Med,Vol 197,No.4,2003 397-401.
2. Fehervari Z et al.J Clin Invest 114:1209-1217(2004).
3. Rudensky A.Nat Immunol 2005.
4. Sakaguchi S.Annu Rev Immunol 2004,22:531-562.
5. Janeway and Travers ,Immunobiology,6th Edition.