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T lymphocytes

T lymphocytes. Contents. 1. Surface markers on T lymphocytes and their function 2. Subsets of T lymphocytes 3. Function of T lymphocytes.

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T lymphocytes

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  1. T lymphocytes

  2. Contents 1. Surface markers on T lymphocytes and their function 2. Subsets of T lymphocytes 3. Function of T lymphocytes

  3. T cells are composed of a group of functionally different and heterogeneous lymphocytes. They are so called because they differentiate and mature in thymus. Mature T cells emigrate thymus and reside in paracortical area of lymph node and around small arteries of spleen white pulp in peripheral lymphoid tissue. T cells execute specific cellular immune response and play an important role in TD-Ag induced humoral immune response.

  4. Molecules on T lymphocytes surface 1. CD molecules associated with T cell recognition, adhesion and activation Common CD molecules T cell

  5. 1.TCR-CD3 complex TCR can be divided into TCRαβand TCRγδ. Structural similarity Transmembrane molecules consisting of two heterodimer chains linking by disulfide bond Each of the polypeptide chains containing variable and constant regions like those of IG

  6. TCR-CD3 complex It is a complex composed of T cell antigen receptor and a group of CD3（γδεζη）molecules binding through noncovalent bonds. It is the major unit of T cells in antigen recognition and signal transduction. TCR specifically recognizes peptides presented on MHC molecules. CD3 transduces the signal 1 of T cell activation.

  7. CD4 andCD8 • CD4 is mainly expressed on mature Th cells, macrophages and DC. It is HIV receptor. It binds the nonpolymorphic region of MHC-II. • CD8 is mainly expressed on mature Tc cells and binds the nonpolymorphic region of MHC-I. • They can not only strengthen the interaction between T cells and APC or target cells, but also stimulate TCR-CD3 signal transduction.

  8. CD4 and CD8 – T cell coreceptor To strengthen the interaction between T cells and APC or target cells To bind p56lck tyrosine-protein kinase via its cytoplasmic CxCP motif, involve in the signal transduction that leads to T cell activation and proliferation

  9. 3. Costimulatory signal molecules Costimulatory signal molecules TCR-CD3 complex provides signal 1. Costimulatouy signal or signal 2 CD28--CD80/86 is the main costimulatory signal participating in T cell activation. CTLA4--CD80/86 provides inhibitory signal for activated T cells.

  10. 1. CD28 and CTLA-4 T APC CD28 CD80/86 CTLA4 CD40L CD40 LFA－1 ICAM－1 LFA－2 LFA－3

  11. Main accessory molecules between T cells and APC

  12. 2、ICOS 3、CD40L 4、CD2 5、LFA-1 and ICAM-1

  13. 4. Other receptors • Mitogen receptors • Cytokine receptors • Virus receptors

  14. 2. T cell differentiation and development

  15. Thymic microenvironment is the essential factor that induces and controls T cell differentiation and development. • Thymic stromal cell （TSC） • Cytokine • Thymic hormone

  16. Double negative stage pro-T、pre-T αβTCR－ 、CD3 － 、CD4 － 、CD8 － Double positive stage αβTCR ＋ 、CD3low、CD4 ＋ 、CD8 ＋ Single positive stage αβTCR ＋ 、CD3 ＋ 、CD4 ＋ αβTCR ＋ 、CD3 ＋ 、CD8 ＋ Mature T cells can recognize antigen, mediate immune response and participate in immunoregulation.

  17. 1. Positive selection of T celldevelopment CD4+CD8+T cell＋TSC（surface MHC molecules） Differentiate into CD8+T cell when bind to MHC-I Differentiate into CD4+T cell when bind to MHC-II Undergo apoptosis in thymic cortex if they do not bind to MHC The positive selection of thymocytes endows mature T cells with MHC restriction in antigen recognition.

  18. Negative selection of T cell development DP or SP T cells after positive selection T cell clones will undergo apoptosis whose TCR can bind MHC or MHC-self antigenic peptides on thymic stromal cells with high affinity. To eliminate autoreactive T cell clones and acquire central tolerance after negative selection

  19. Negative selection (to acquire self tolerance Positive selection (to acquire MHC restriction) Migrate to peripheral blood and lymphoid organ Apoptosis Self peptide Apoptosis Thymic stromal cells Apoptosis Positive and negative selection of T cell repertoire in thymus

  20. 3. T subsets 1）TO divide into αβT、γδT subsets according to TCR type In peripheral blood ,αβT cells account for 95% whileγδT cells range from 1% to 10%。The two subsets of T cells have different characteristics and functionl.αβT cells are the main T cells participating in immune response.

  21. TCRαβT and TCRγδT cells TCRαβT TCRγδT low diversity 5-15％, mucosal epithelia mature, mostly CD2CD3 simple polypeptide, HSP, lipid, polysaccharide MHC like molecules Tc TCR Distribution Phenotype Antigen recognition MHC restriction Function high diversity 60-70％, peripheral lymphoid tissue mature, CD2CD3CD4/CD8 8－17aa classical MHC Th、Tc

  22. 2） To divide to CD4+ T cells or CD8+ T cells according to whether T cells express CD4 or CD8 TCRαβTCD4+ cells：CD2+、CD3+、CD4+、CD8- TCR antigen recognition is MHCⅡrestrictive. Display Tc、Ts function. TCRαβTCD8+ cells：CD2+、CD3+、CD4-、CD8+ TCR antigen recognition is MHC I restrictive. Display Tc、Ts function.

  23. 3）Functional subsets：Th、Tc、TDTH、Ts • Th cells can be divide into Th0、Th1 and Th2 subsets according to cytokine secretion. • Tc cells cytotoxicity, to secrete IFN, IL-4, IL-5 and IL-10 • Ts cells • TDTH is mainly CD4 + Th1

  24. 4）Primary T cells and memory T cells Memory T cells express CD45RO while primary T cells express CD45RA 5）NK1.1 T cells Their TCR recognize lipid and liposaccharide antigen presented by CD1 molecule.

  25. 4. T cell function . 1）Immunoregulation（Th1、Th2、Ts） 2）Specific cytotoxicity（CTL、Th1、γδT） 3）Mediate hypersensitivity（TDTH）

  26. 1. CD4＋ accessory T cells 2. CD8＋cytotoxic T cells

  27. Regulation of cytokine on Th1 andTh2 cells

  28. Cytotoxic T cells Accessory T cells Inflammatory T cells Cytokine Cytokine Perforin Granzyme Target cell Intracellular bacteria Others MAF Others Others Effector molecules B cell activation factor Schematic diagram of effector molecules produced by 3 kinds of effector T cells

  29. 3. Suppressor T cells 4. Delayed hypersensitive T cells（TDTH） 5. NK1.1＋T cells

  30. Master the types and structure of TCR • Master T subset categories and the biological features of different subsets • Master the developmental process of T cells • Familiarize the main membrane molecules on T cell surface and their function • Understand the similarity and differnce between TCRγδT cells and TCRαβT cells

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