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Cytokines in Hematopoeisis & Development

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Cytokines in Hematopoeisis & Development cytokines in INTRODUCTION In the fetus, commiitted hematopoiietiic stem celllls devellop iin the mesoderm and miigrate to Hematopoiesis the fetall lliiver iin the 6th week of pregnancy. Fetall lliiver stem celllls then iiniitiiate erythropoiiesiis and seed the devellopiing thymus (iin Development week 7) and bone marrow (iin week 20).1-3 In the thymus, αβ and γδ T celllls devellop, and the Committed potentiiall allso exiists for variious Hematopoetic Cell Mouse Mφ = Kupffer Cell Formation ((rreff.. 77,,78,,79)) dendriitiic celllls (DC) and naturall F4//80+ killer (NK) cell types. In the bone CD34++ killer (NK) cell types. In the bone F4//80+ To Liiver CD38-- CD7-- marrow, B celllls, granullocytes, CD44++ GM-CSF CFU--GM SCF R//c-Kiitt+ + monocytes and DC all potentially Mesodermal Mφ ER--MP12 Flltt-3+ monocytes and DC all potentially primitive ((rreff.. 1,,2,,3)) macrophage Mφ M-CSF devellop. Thiis pattern persiists in yolk sac Monoblast wellll iinto adullthood. ER-MP20+ Fetal Mφ HSA//CD24-- Mφ ? Fetal Liver To the Liver CD34++ Stem Cell Kupffer Cell CD38-- CD7+//-- CD44++ SCF R//c-Kiitt+ Flltt-3+ CD33+ CD43+ CD2-- CD10-- Thy-1//CD90+ CXCR4+//-- ((rreff.. 1,,4,,5)) CD34++ CD2-- - - s CD38- CD10- us +//-- + week 7 m CD7 CD90//Thy-1 ym ++ ++≠ h + Multipotential CD44 CXCR4 T CD34+ SCF R//c-Kiitt+ To CD4+ Thymic CD33+ CD7-- Precursor CD43+ -- week 20 CD34+ CD3 + -- ++ - CD4+ CD34 CD45RA CD34++ CD5- T w + -- -- To Bone Marro CD45RA+ CD4 (reff.. 16) CD38 CD1a + ++ + IIL-3 Rα+ CD45RA CD7++ CD45RA+ 5)) ++ + IIL-6,, SCF//c-Kiitt Liigand ((rreff.. 5 CD11c+ Flltt-3 CD44 IIL-7 Rα Flt-3 ΙΙ+ Flt-3 Liigand Nottch-1+ ((rreff.. 4,,6,,7)) MHC- Liigand CD33+ CD2-- 83 FL Delltta B cell Development in Mouse; an exact parallel? Flltt-3 Prolliifferattiion B cell Development in Mouse; an exact parallel? Liigand Jagged IIL-7 PPBSF ((rreff.. 35,,36)) IIL-7 ((rreff.. 37,,41)) TSLP ((rreff.. 38,,39)) SCF//c-Kiitt Liigand SCF//c-Kiitt Liigand CD34-- TLR7+ Thymic DC GM-CSF SDF-1 CD4+ TLR9+ IIL-6 T / NK Precursor CD45RA+ BDCA-2+ CD34+ T / NK Progenitor IIL-3 Rα+ ((rreff.. 16,,17,, Pro-DC2 CD7++ B-Lymphoid CD11c-- 18,,19)) IIL-2 Rβ+ CD34++ CD5+ Progenitor B cell Pre-Pro B cell Pro B cell Pre B cell Immature MHC-ΙΙ+ CD38+ CD38+ CD1a-- ((rreff.. 33,,34,,40)) ((rreff.. 33,,34,,40)) ((rreff.. 33,,34,,40)) ≠ Progenitor B cell ((rreff.. 33,,34,,40)) CD161//NKRP1A+ CD7++ CD45RA++ + +↓ + CD34 CD34+ Flltt-3+ CD34+//-- CD19-- CD43+ CD24+ CD43-- CD24+ CD43-- CD24+ ((rreff.. 7,,9,,11)) CD44+ IIL-7 Rα+ + lo CD43 CD43+ CD19-- CD43+ CD24+//-- CXCR4+ CD25-- CXCR4+ CD25+ CXCR4+ CD25+ CD33lo ((rreff.. 4,,6,,7)) + + CD10 CD10+ CD24// CXCR4+ CD25-- IIL-7 Rα+ CCR9+ IIL-7 Rα+ CCR9-- IIL-7 Rα-- CD2+ CD2+ CD45RA+ -- CD40L Pre-NK CXCR4+ HSA IIL-7 Rα+ CCR9+ SCF R// CXCR5+ SCF R// CXCR5+ SCF R// CD72+ Pre-DC2 Pre-NK -- + +//-- -- IIL-3 CD90//Thy-1 IIL-7 Rα+ CD25// SCF R// c-Kiitt c-Kiitt c-Kiitt CCR9-- Cell TdT+ IIL-2 Rα-- -- + -- -- SCF R// c-Kiitt TdT TdT TdT CXCR5+ viirus ((rreff 20)) α+ + + + -- -- Immature DC2 IIL-7 IIL-7 R c-Kiitt TdT Flltt-3 Flltt-3 Flltt-3 Flltt-3 Liigand CD34++ α//β+++ ((rreff.. 30,,31)) TdT+ Flltt-3+ CD19+ CD19+ CD19+ IIFN- + ↓ IIL-7 CD38 Pre-T1 CD34+↓ CD5+ ++ IIL-15 CD7 CD38+ CD1a+ ++ ((rreff.. 7,,10,,11)) CD44 CD7+↓ CD45RA+↓ IIL-2 CD30llo IIL-7 & Flltt-3 CD34-- CD30 CD44+ IIL-7 Rα+ Liigand IIL-12 CD2+ CD7++ CD2 CD33-- ((rreff.. 6,,7)) ((rreff.. 83)) Pro-B cell / + CD5+ IIL-7 iis suggestted tto be lless CD58 IIL-2 Rβ+ CD5 CD2+ Pre-B-Ι cell + Pre-B- cell criittiicall tto B cellll devellopmentt iin CD54+ + CD1a ((rreff.. 31,,32)) CD161 + (ref. 76) + CD45RA++ CD34 man tthan iin mouse.. (ref. 76) CD80 CD56+ CD45RA + Pre-B cell / + CD43 CD86 ((rreff.. 7,,9,,11)) Immature Pre-B-ΙΙ cell ((rreff.. 31,,32)) + IL-7 CD10++≠ MHC-ΙΙ+ NK Cell IL-7 CD45RA+ ((rreff.. 17,,18)) CD34-- CD1a+ CD45RA IIL-3 ((rreff.. 81,,82)) + Pre-T2 / CD4+ + -- TdT IL-7 Immature B cell CD38 CD45RA +/- IL-7 + + IIL-7 Rα+/- ((rreff.. 32)) IIL-12 Immature CD7+ CD4+ CD34-- Mature B cell ((rreff.. 32)) IL-18 CD44-- CD8α-- (CFU-BLAST) CD34 IL-18 CD44 CD8 CD43+ CD2+ CD8β-- Primitive Stem Cell CD40L ((rreff.. 81)) CD16varriiablle Primitive Stem Cell Prolliifferattiion iinduced by:: CD10+↓ CD16 CD5+ IIL-3 CD2+ Flltt-3 Liigand CD45RA++≠ CD2 CD7++ Mature NK Tpo TdT-- + CD7 TdT CD10 + SCF//c-Kiitt Liigand - IIL-2 Rβ+ Cell IIL-7 Rα- CD19+ CD10+ IIL-3 CD56+ γδ T cells IIgM+ CD19+ ((rreff.. 54,, 58)) ((rreff.. 7,,11)) IIgM+ SCF//c-Kiitt Liigand Early Double- CD34++ ((rreff.. 66)) + IL-2 Resttiing IIgD IL-2 positive CD38-- - Thymocyte CD7+ CD4+ CD71-- CD34- Stem Cell CD2+ CD8α+ CD33+ Stem Cell CD34+ ((rreff.. 12,,13)) (iin adulltt) CD5+ CD8β-- CD10-- G + -- 10% of Blood CD10 G CD33 CD71 + -CSF ++ CD1a+ ((rreff.. 6,,7)) CD5-- CD13-- ++ NK Cells CD56 (ref. 67,68) gllycophoriin CD45RA-- CD90+/Thy-1+ (ref. 67,68) ΙΙ+ CD16-- CD45RA CD90 /Thy-1 MHC- *CFU-E’’s are allmostt T200+//-- CD45RA-- -- T200+ SCF R//c-Kiitt+ CD10 iindiisttiinguiishablle ffrom (ref. 59) ++ (ref. 59) Late Double- ((rreff.. 30,, 46,, 47,, 69,, 70)) Thy-1//CD90-- BFU-E (reff.. 60).. CFU-E CD71 + -- -- CD34 CD33 gllycophoriin++ positive + + TGF-β CD45RA are reportted tto show a CD7 CD4 TGF- + + -- CD56+ CD38+ CD71 gllycophoriin slliightt reducttiion iin (reff.. 59) CD56 Thymocyte CD2+ CD8αβ+ ((rreff.. 24)) -- ++ CD16++ GEMM ((rreff.. 30,,43,,44,,45,,46)) CD45RA T200 MHC-ΙΙ (reff.. 60) and a CD16 CD5+ CD69-- SCF R/c-Kit+++ MHC-ΙΙ+ Reticulocyte SCF R/c-Kit-- SCF R/c-Kit MHC- slliightt iincrease iin CD71 Epo SCF R/c-Kit CD1a+ ((rreff.. 6,,7)) + CD38 (reff.. 59).. IIL-3 LAK Cell IIL-2 CD45RA-- ((rreff.. 14)) (reff.. 55) CD45RO+ SCF//c-Kiitt Liigand TGF-β CD25+ IIL-3 GM-CSF ΙΙ+ ((rreff.. 24)) Pronormoblast MHC-ΙΙ IIL-4 IIL-12 IIL-9 Epo FGF-2 ((rreff.. 15)) Epo ((rreff.. 55)) ((rreff.. 25)) + ((rreff.. 55,, 57,, 80)) CD1a Tpo R+ + -- IIL-5 & IIL13 CD4+ CD1a CD45RA Tpo -- + + CD34 NK2 Cell secrettiion + CD4+ CD45RO+ IIL-6 CD8α//β CD41+ no IL-4 -- + no IL-4 CD69+ CD8 CD69 ((rreff.. 62)) CFU-E + CD69 IIL-3 BFU-E CD42 CD27-- ((rreff.. 6,,7)) + IIL-11 CD32 GM-CSF ΙΙ-- CD1a+ (ref. 71) IIL-3 MHC-ΙΙ IIFN-γ IIL-3 (ref. 71) + GMCSF ((rreff.. 71,, 73)) secrettiion CD69 SCF//c-Kiitt Liigand + Tpo CD27 Flltt-3 Liigand NK1 Cell Endstage + IIL-6 Endstage CD4 ((rreff.. 55,,57)) + ((rreff.. 63,,71)) Tpo Cell CD8 + CFU-GM IIL-11 CD1a (reff 6,,7) + ((rreff.. 75)) CD69 Functional CD27+ CD34+ + CD4-- CD4 T Cell CD33++ 90% of Blood CD8+ -- CD38+ CD34+ CD1a NK Cells (reff 6,,7) + SCF R// SCF R// TGF-β CD4 c-Kiitt+//-- c-Kiitt+ ((rreff.. 24)) CD8-- + + CD69+ CD45RA Tpo R CD1a-- CD69 -- BFU-MK ΙΙ-- CD45RA+ IIL-3 CD10 MHC- CD69+ CD45RA SCF//c-Kiitt Liigand CD54++ CD41-- CD45RO-- CD54 GM-CSF ΙΙ+ Tpo CD27+ (ref. 48) + -- MHC-ΙΙ + (ref. 48) CD13+ IIL-3 CD45RA -- CD27 Tpo R+ IIL-11 Megakaryocyte CD4 ((rreff.. 43,,44,,52,,53)) SCF//c-Kiitt Liigand ((rreff.. 71,,72,,73)) CFU-MK Functional + ((rreff.. 6,,7)) CD41llo CD45RA-- ((rreff.. 75)) CD8 ((rreff.. 55)) + -- M-CSF CD61+ CD42-- CD8 T Cell CD45RO + -- CD45RA+ ((rreff.. 54,,55)) IIL-3 CD34 CD32 IIL-10 ((rreff.. 54,, 61,, 71,, 72,, 73,, 74)) IFN-γ ((rreff.. 56)) IL IFN- CFU-G Platelets IL-12,, IIL-27 ((rreff.. 26)) anttiigen CFU-MAST G-CSF ++ G-CSF TGF-β CD33 IIL-3 CD34+ CD45RA++ Tr1 ((rreff.. 27,,28)) CD45RA ((rreff.. 55,,56)) Neutrophilic 23 + + L-4 L-- CD13 CD13+ IIL ,, II Myelocyte 8 + + CFU-M -- -- Myelocyte --1 CD4+ SCF R//c-Kiitt CD24 CD66 Th1 IIL ↓ ,, + FcεRII-- -- ++ CD33++↓ 2 (CD25+ ??) CD10 CD54 or --1 + -- IIL γ CD33 -- CD45RA , IIL-10 & IIFN- CD11b ((rreff.. 52,,44)) ↓ γγ, SCF R/ + + - ΙΙ+ SCF R/ + CD10 CD33 - no IL-4 or IL-2 MHC-ΙΙ llo CD11b N no IL-4 or IL-2 c-Kiitt G-CSF + -- FF + +/-↓ CD11b CD45RA II B7 CD38+ + CD54+/- CD13+ ((rreff.. 55,,56)) + +//-- - ++ CD24 CD54 IICOS-L + Trypase- + CD66++ CD4+ CD45RA+ ++ -- + CD66 Th2 IIL-4 ++ Chymase CD33+ CD24 CD25 + ((rreff.. 48,, 50)) MHC-ΙΙ+ CTLA-4 M-CSF -- CD2+//-- CD45RA CD7+//-- SCF//c-Kiitt Liigand Dendritic Cell CD34-- IIL-6 CD34 Th3 Cell CD2-- CD86-- ((rreff.. 49,,50)) ((rreff.. 43,,44,,54)) Th1 CD11b+ CD45RA-- CD14+++ TRL2+ CD2+ Neutrophil CD33+ TRL4+ (Immature?) CD11b+ CD40-- TRL5+ MAST CELL (MC ) CD14+++ Th2 T CD80-- TRL8+ CD33+ Immunosuppression by regulatory CD34-- ((rreff.. 42,,16,,17)) Immunosuppression by regulatory CD40-- CD13+ T celllls iis suggested to iinvollve cellll- CD80-- + SCF R//c-Kiitt+ to-cellll contact. In miice, CD25+ CD86-- FcεRII-- regullatory T celllls are reported to ((rreff.. 42)) CD33+ have cellll surface TGF-β, whiich + CD38+ Monocyte / may mediiate thiis effect (ref. 29). MHC-ΙΙ-- Pre DC1 Trypase+ Chymase-- + ((rreff.. 48,,50,,51)) CD1a+ CD80+ CD32+ CD54+ IL-5 CD54 IL-5 + IIL-4 ((rreff.. 48)) CD11c MHC-ΙΙ+ GM-CSF ((rreff.. 64,,65)) IIL-4 ((rreff.. 21,,22)) M-CSF Potential Langerhans Cell Developmental Pathway (abbreviated) (reff.. 17,, 23) Immature DC1 Precursor CD34+ CD34-- Macrophage GM-CSF CD10+ FcεRII-- TNF-α CXCR4+ SCF R//c-Kiitt-- MAST CELL (MCTc) MHC-ΙΙ-- Trypase+ Chymase+ CD40L CD14-- (reff.. 50,,51) TNF-α CLA+ CD72+ CD11c+ CD1a+ Mature DC1 TGF-β CD14-- MHC-ΙΙ+ CD86+ CD38+ + Langerhans Cell CD40 ((rreff.
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