分子免疫学-T细胞亚群
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Effector memory T cells
do not express CCR7 or L-selectin, and home to peripheral tissues, especially mucosa.
produce effector cytokines upon antigenic stimulation do not proliferate much.
None
Cell cycling
No
Surface protein expression
High-affinity IL-2
Low
receptor
Peripheral lymph
High
node homing receptor
(L-selectin, CD62L)
Adhesion molecules: Low integrins, CD44
Effector T cells （效应T细胞） Memory T cells （记忆T细胞） T helper (Th) 辅助性CD4+T细胞 Cytotoxic T cells (CTLs) 细胞毒性CD8+T细胞 Regulatory T cells (Tregs) 调节性CD4+T细胞
T Cell subsets
Nature Immunol, 2011, June, the reviews of memory T cell
CD4+ CD8+ CD4+
Effector T cell subsets
.
Discovery of CD4+ Th cell subsets
Th1-Th2 hypothesis 1986 Coffman and Mossman
Naive T cells Effector T cells Memory T cells
Migration
Frequency of cells responsive to particular antigen Effector functions
Preferentially to peripheral lymphoid tissues Very low
Class
αβ T lymphocytes
CD4+ helper T lymphocytes
Functions
B cell differentiation (humoral immunity) Macrophage activation (cellmediated immunity)
Antigen receptor and specificity
Memory T cells
Long-lived, functionally silent cells; Mount rapid secondary immune responses to the same antigen
exposure Heterogenous (central and effector)
Ag recognition by TCR
GATA-3
Development of Th1 and Th2 subsets
Th2 cell differentiation requires both GATA3 expression and STAT5 activation
STAT: Signal transducer and activator of transcription
Differentiation of Th1 Subset
Stimulated by intracellular microbes that infect or activate macrophages or NK cells
The molecular basis of Th1 differentiation
The interplay of signals from the T cell receptor, the cytokines IFN- and IL-12, and the TF T-bet, STAT1, and STAT4
IL-12
STAT-4
IFN-
STAT-1
Ag recognition by TCR
T-bet
A positive amplification loop between T-bet and IFN-
Differentiation of Th2 Subset
Stimulated by microbes and antigens that cause persistent or repeated T cell stimulation with little inflammation or macrophage activation Helminth and allergens
Selected markers
Percent of total lymphocytes (human)
Blood
αβ heterodimers Diverse specificities for peptide-class II MHC complexes
CD3+, CD4+, CD8-
50-60*
αβ heterodimers Diverse specificities for peptide-class I MHC complexes
Suppress function of other T cells (regulation of immune responses, maintenance of selftolerance)
T 细胞亚群 T 细胞活化机制 T 细胞免疫应答及其效应
Phases of T cell responses priming
T cell subsets
T cells (~95%) and T cells (~5%) CD4+T cells and CD8+T cells Naïve T cells（初始T细胞）
αβ heterodimers
Helper and cytotoxic functions (innate immunity)
γδ heterodimers Limited specificities for peptide and nonpeptide antigens
CD3+, CD4-, CD8+ 20-25
Th17
2005
Tfh
2000
The subsets of CD4+Th cells
Humoral Immunity
Th0
Th1
Th2
Th17
How theyBiblioteka Baiduare induced, What cytokines they produce What effector mechanisms they activate
Chemokine receptor: High CCR7
Major CD45 isoform (humans only)
CD45RA
Morphology
Small; scant cytoplasm
Preferentially to inflamed tissues High
Cytokine secretion; cytotoxic activity Yes
Important cytokines for the Th2 differentiation IL-4
Important TF for the Th2 differentiation GATA-3: master regulator STAT6
The molecular basis of Th2 differentiation
where they recognize antigen
Effector T cells
Activated T cells capable of performing the functions required to eliminate foreign antigens
Preferential migration to sites of infection or inflammation Short-lived
Lymph node
50-60
Spleen 50-60
CD8+ cytotoxic T lymphocytes
Regulatory T cells
γδ T lymphocytes
Killing of cell infected with microbes, killing of tumor cells
Phases of T cell responses priming
Based on the history of antigen encounter and the stage of T cell activation.
Naïve T cells
Mature T cells that have not previously encountered antigen; Preferential migration to secondary lymphoid organs (lymph nodes),
CD3+, CD4+, CD25+ (Most common, but other phenotypes as well)
Rare
CD3+, CD4, and CD8 variable
15-20 10
10-15 10
T cell development in the thymus
Positive selection Negative selection
The interplay of signals from the T cell receptor, the cytokine IL-4, and the TF GATA-3 and STAT6
Th2 differentiation is most dependent on IL-4
IL-4
STAT-6
Immune modulation
Properties of CD4+ Th1 and Th2 subsets
Stimuli that influence the pattern of Th cell differentiation
Cytokines TCR signal strength Different subsets of dendritic cells may exist The genetic makeup of the host
High Low
High Low CD45RO Large; more cytoplasm
Preferentially to inflamed tissues, mucosal tissues Low
None +/-
Low Low or variable
High Variable CD45RO; variable Small
Subsets of memory T cells
Based on their homing properties and effector functions.
Central memory T cells
express CCR7 and L-selectin, and home to lymph nodes. limited capacity to perform effector functions when they encounter antigen generate many effector cells upon antigen challenge
Listeria, mycobacteria and Leishmania
Important cytokines for the Th1 differentiation IL-12 IFN- IL-18 type I IFNs (in human)
Important transcription factors (TF) for the Th1 differentiation T-bet: master regulator STAT4 STAT1
do not express CCR7 or L-selectin, and home to peripheral tissues, especially mucosa.
produce effector cytokines upon antigenic stimulation do not proliferate much.
None
Cell cycling
No
Surface protein expression
High-affinity IL-2
Low
receptor
Peripheral lymph
High
node homing receptor
(L-selectin, CD62L)
Adhesion molecules: Low integrins, CD44
Effector T cells （效应T细胞） Memory T cells （记忆T细胞） T helper (Th) 辅助性CD4+T细胞 Cytotoxic T cells (CTLs) 细胞毒性CD8+T细胞 Regulatory T cells (Tregs) 调节性CD4+T细胞
T Cell subsets
Nature Immunol, 2011, June, the reviews of memory T cell
CD4+ CD8+ CD4+
Effector T cell subsets
.
Discovery of CD4+ Th cell subsets
Th1-Th2 hypothesis 1986 Coffman and Mossman
Naive T cells Effector T cells Memory T cells
Migration
Frequency of cells responsive to particular antigen Effector functions
Preferentially to peripheral lymphoid tissues Very low
Class
αβ T lymphocytes
CD4+ helper T lymphocytes
Functions
B cell differentiation (humoral immunity) Macrophage activation (cellmediated immunity)
Antigen receptor and specificity
Memory T cells
Long-lived, functionally silent cells; Mount rapid secondary immune responses to the same antigen
exposure Heterogenous (central and effector)
Ag recognition by TCR
GATA-3
Development of Th1 and Th2 subsets
Th2 cell differentiation requires both GATA3 expression and STAT5 activation
STAT: Signal transducer and activator of transcription
Differentiation of Th1 Subset
Stimulated by intracellular microbes that infect or activate macrophages or NK cells
The molecular basis of Th1 differentiation
The interplay of signals from the T cell receptor, the cytokines IFN- and IL-12, and the TF T-bet, STAT1, and STAT4
IL-12
STAT-4
IFN-
STAT-1
Ag recognition by TCR
T-bet
A positive amplification loop between T-bet and IFN-
Differentiation of Th2 Subset
Stimulated by microbes and antigens that cause persistent or repeated T cell stimulation with little inflammation or macrophage activation Helminth and allergens
Selected markers
Percent of total lymphocytes (human)
Blood
αβ heterodimers Diverse specificities for peptide-class II MHC complexes
CD3+, CD4+, CD8-
50-60*
αβ heterodimers Diverse specificities for peptide-class I MHC complexes
Suppress function of other T cells (regulation of immune responses, maintenance of selftolerance)
T 细胞亚群 T 细胞活化机制 T 细胞免疫应答及其效应
Phases of T cell responses priming
T cell subsets
T cells (~95%) and T cells (~5%) CD4+T cells and CD8+T cells Naïve T cells（初始T细胞）
αβ heterodimers
Helper and cytotoxic functions (innate immunity)
γδ heterodimers Limited specificities for peptide and nonpeptide antigens
CD3+, CD4-, CD8+ 20-25
Th17
2005
Tfh
2000
The subsets of CD4+Th cells
Humoral Immunity
Th0
Th1
Th2
Th17
How theyBiblioteka Baiduare induced, What cytokines they produce What effector mechanisms they activate
Chemokine receptor: High CCR7
Major CD45 isoform (humans only)
CD45RA
Morphology
Small; scant cytoplasm
Preferentially to inflamed tissues High
Cytokine secretion; cytotoxic activity Yes
Important cytokines for the Th2 differentiation IL-4
Important TF for the Th2 differentiation GATA-3: master regulator STAT6
The molecular basis of Th2 differentiation
where they recognize antigen
Effector T cells
Activated T cells capable of performing the functions required to eliminate foreign antigens
Preferential migration to sites of infection or inflammation Short-lived
Lymph node
50-60
Spleen 50-60
CD8+ cytotoxic T lymphocytes
Regulatory T cells
γδ T lymphocytes
Killing of cell infected with microbes, killing of tumor cells
Phases of T cell responses priming
Based on the history of antigen encounter and the stage of T cell activation.
Naïve T cells
Mature T cells that have not previously encountered antigen; Preferential migration to secondary lymphoid organs (lymph nodes),
CD3+, CD4+, CD25+ (Most common, but other phenotypes as well)
Rare
CD3+, CD4, and CD8 variable
15-20 10
10-15 10
T cell development in the thymus
Positive selection Negative selection
The interplay of signals from the T cell receptor, the cytokine IL-4, and the TF GATA-3 and STAT6
Th2 differentiation is most dependent on IL-4
IL-4
STAT-6
Immune modulation
Properties of CD4+ Th1 and Th2 subsets
Stimuli that influence the pattern of Th cell differentiation
Cytokines TCR signal strength Different subsets of dendritic cells may exist The genetic makeup of the host
High Low
High Low CD45RO Large; more cytoplasm
Preferentially to inflamed tissues, mucosal tissues Low
None +/-
Low Low or variable
High Variable CD45RO; variable Small
Subsets of memory T cells
Based on their homing properties and effector functions.
Central memory T cells
express CCR7 and L-selectin, and home to lymph nodes. limited capacity to perform effector functions when they encounter antigen generate many effector cells upon antigen challenge
Listeria, mycobacteria and Leishmania
Important cytokines for the Th1 differentiation IL-12 IFN- IL-18 type I IFNs (in human)
Important transcription factors (TF) for the Th1 differentiation T-bet: master regulator STAT4 STAT1