T-Lymphocytes
Function, Development, Subpopulations
Activation of T-lymphocytes
• T-lymphocytes can be stimulated only by
complexes of antigen-HLA antigen.
• The HLA antigen must be the same as HLA
antigens of the person from whom the
lymphocytes originate= phenomenon of HLA
restriction.
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Interaction TCR-polypeptide-HLA molecule
Thymic education
• Positive selection: survival of cells reacting with
low affinity with HLA antigens expressed on
antigen-presenting cells in the thymus. Only those
cells that recognize HLA antigen of the concrete
person survive. The non-reacting cells die by
neglect.
• Negative selection – those thymocytes that react
with high affinity with complexes of HLAautoantigens
in thymus die by apoptosis.
• It is supposed that more than 90-95% of
thymocytes die during these processes.
Development of lymphocytes in the
thymus
The Fate of T-lymphocytes in the Thymus
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Thymic education of lymphocytes
Strength of interaction between TCR and HLA-(antigen)
complexes determines the fate of thymocytes
Neglected cells Positive selectoion Negative selection
Stength of interaction
Cell death
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V, D and J genes involved in T- and B- cell receptor formation
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Activation and differentiation of T-lymphocytes
Central role of T-lymphocytes in specific immune
response
Antigen-presenting cell
Antigen
Th
cell
B
cell
Tc cell Granulocyte
Macrophage
NK
NK cell
Subpopulations of T-lymphocytes
• Cytotoxic T-lymphocytes (CD8+): kill target cells.
Activated by complex HLA-I –antigenic peptide.
• Helper T-lymphocytes (CD4+): enable activation
of macrophages (Th1) or B-cells (Th2) cells. They
are activated by complexes HLA-II- antigenic
peptide.
• Regulatory T-cells (CD4+): important in the
maintenance of immune tolerance.
Subpopulations of Th-lymphocytes
• Th1 lymphocytes
– Produce IFN-g, IL-2, IL-3,
– Stimulation of macrophages, pro inflammatory
effect
– Probably pathogenic in multiple sclerosis…
• Th2 lymphocytes
– Produce IL-3, IL-4, IL-5, IL-6, IL-10, IL-13
– Stimulation of antibody production, including IgE
– Included in pathogenesis of allergic diseases
• Th17 lymphocytes
– Produce IL-17
– Important in chronic inflammation
Also Th9, Th22lymphocytes
Functions of T-lymphocytes
Development of Th1 and Th2 cells
Bacteria
TH 1
TH 0
TH 2
Macrophage
NK cell Mast cell
Function of TH1 and Th2 cells
Mast cell
Macrophage
Inhibits production
Th1
cell
Th2
cell
B
cell Eosinophil
Cytokine environment decides the future development of Th0 cells
Th1 lymphocytes
• Secretion of IFN-g, IL-2, IL-3.
• Differentiate after stimulation by IL-12, IL-18, IFN-g
• Pro-inflammatory effect, stimulate function of
macrophages.
• Involved in pathogenesis of multiple sclerosis…
• Down-regulation of Th2 cells by production of IFN-g
• Involved in accute graft rejection
Function of Th1 cells
Th2 lymphocytes
– Secrete IL-3, IL-4, IL-5, IL-6, IL-10, IL-13
– Differentiate after stimulation by IL-4
– Stimulation of antibody production, including
IgE
– Included in pathogenesis of allergic diseases
– By production of IL-10 suppress function of
Th1 cells.
– Th2 predominance in pregnancy.
Th2-lymphocytes are essential for stimulation of B-lymphocytes
Th 17 cells
• Important in protection against bacteria and
fungi.
• Differentiate after stimulation by IL-1b,
TNFa
• Secretion of IL-17, IL-22, IL-23.
• Pathology – involved in chronic
imfammatory states, including rheumatoid
artritis, Crohn disease.
Cytotoxic T-lymfocytes
• CD8+
• Foreign antigens are recognized in complex
with HLA-I class antigens.
• Mechanism of cytotoxicity: perforin
(induction of membrane pores), various
mechanism inducing apopsosis of the target
cell (granzymes, FasL, lymfotoxin).
• Produce various cytokines (Tc1 and Tc2
cells)
Cytotoxic effect of CD8+ cells
CD8 lymphocytes induce apoptosis of target cells
IL-10
Types of regulatory T-lymphocytes
Periphery
From: Nature Immunology
Treg lymphocytes
• Thymic development
• Express CD4+CD25+
• Involved in tolerace of autoantigens
• Comprise approximately 5-10% of peripheral
CD4+ lymphocytes
• Can be incuced also in periphery by foreign
antigens.
TR-1 Lymphocytes
• Antigen-induced regulatory CD4+ cells.
• Develop from antigen stimulated Tlymhocytes
in the environment of IL-10.
• Tolerance of foreign antigens.
• Very similar are „Th3 cells“.
T- and B-cells antigen-speciphic receptors
gd-T-lymphocytes
• Comprise approximately 5% of peripheral
lymphocytes.
• CD3+, CD4-CD8•
Low antigenic specificity.
• Thymus in not necessary for their development.
• Other than HLA antigens may be involved in antigen
presentation.
• Increased in mycobacterial infections, Erlichiosis,
listeriosis.
Intraepitelial T-lymphocytes
• TCR of ab or gd type
• Low antigenic specificity
• Extrathymic differentiation
• The first line of the specific immune
response
• Usually CD8+