Cell type Date of discovery and naming in the first publish Main development location Major transcription factors and molecules needed for development Anatomical locations Developmental stage that derived from common progenitor Major cytokines produced by cells Major stimulating cytokines Activator and proliferator cells Antigen receptor Ligands Major surface markers MHC/MHC-like restriction Major functions and pathology Antimicrobial defense mechanisms Reference
MAIT
(i) Porcelli et al. 1993 [3 ] (ii) Tilloy et al. 1999 [4 ] Thymus PLZF (ZBTB16) in human (i) Gut lamina propria (ii) Liver (human) (iii) Blood (few numbers) Late double negative (DN) IL-4 IL-5 IL-10 IL-17 IFN-
TNF-
IL-1
(i) B cells (ii) Gut normal flora TCR
/
V
19 (mouse) V
7.2 (human) Hydrophobic molecules IL-12R, IL-18R, IL-23R CD4− CD8− , CD8
+ (human), CD161 (NKR-P1A), NKG2D, NKP30, P80, CCR6, CXCR6 MR1 (class Ib) restriction (i) Possible regulation of inflammation in autoimmune disorders (ii) Regulation of IgA production in gut (iii) Intestinal homeostasis (iv) CNS pathology (i) Cytokine production (ii) Cellular recruitment and recalling (iii) Cytotoxicity (Fas, granzymes) [3 –6 ]
iNKT (i) In mouse: Koseki et al. 1990 [7 ] (ii) In human: Porcelli et al. 1993 [3 ] Thymus PLZF SLAM Peripheral lymph tissues such as liver, spleen, and lymph nodes Double positive (DP) (pro-T) IL-4 IL-10 IL-13 IFN-
TGF-
IL-7 IL-12 IL-25 IL-33 TSLP APCs TCR
/
V
14 (mouse) V
24 (human) Glycolipids especially
-Gal-Cer DN or CD4+ (mouse), DN or CD8+ or CD4+ (human), CD28, ICOS, NK1.1, NKG2D CD1d (i) Immune regulation (ii) Immunity against infection (iii) Graft rejection and GVHD (iv) Pathogenesis of cancers, allergy, and autoimmune disorders (i) Cytokine storm in a few minutes to hours (ii) Cellular recruitment and recalling [3 , 7 –10 ]
/
T cell(i) Saito et al. 1984 [11 ] (ii) Samelson et al. 1985 [12 ] Thymus Sox13 Id3 Egr-1 (i) Epiderm (ii) Mucosal tissues (iii) Blood (few numbers) DN2 IL-17 IFN-
TNF-
IL-2 IL-7 IL-21 (i) Mostly by antigens directly (ii) APCs (less common) TCR
/
Mostly nonpeptidic-self and nonself-antigens NKRs: KIRs and NKG2A, C, D, TLRs, CCR7, CD16, CD226, MHC II, cytokine receptors (i) Mostly no need to MHC restriction (direct recognition) (ii) MHC/MHC-like restriction (less common) (i) Immune regulation (ii) Immunity against infection (iii) Tissue repair (i) Cytokine production (ii) Cellular recruitment and recalling (iii) Cytotoxicity (Fas, granzymes, perforin) [11 –16 ]
MZB MacLennan et al. 1982 [17 ] Spleen marginal zone BAFF Pyk-2 Notch2 (i) Spleen (ii) Blood (few numbers) (iii) Few numbers in Peyer’s patches and lymph node subcapsular sinus T1/T2 (immature B cell) IL-6 IL-10 IFN-β IL-7 IL-21 (i) APCs (ii) Mostly T independent (iii) Directly by antigen (iv) T dependent (less common) BCR: IgMhi IgDlow Mostly nonpeptidic antigens CD1, CD9, CD27, CD36, CD11b, GP49b, TLRs, S1P1, MHC II, FC-like receptors, CD23− CD1 (less common) (i) Immunity against blood-borne infections (ii) Immunity against encapsulate bacteria (iii) Response to autoantigens derived from senescence IgM and IgG3 production [17 –20 ]
B1-B cell (i) Gronowicz and Coutinho 1975 [21 ] (ii) Hayakawa et al. 1983 [22 ] Firstly in BM, then located in tissue BAFF NFATc1 Siglec-G (i) Peritoneal and pleural cavity (ii) Lungs (iii) Blood (few numbers) T1/T2 (immature B cell) IL-6 IL-10 TNF-
IL-5 (i) Mostly T independent (ii) Directly by antigens BCR: IgMhi IgDlow Mostly nonpeptidic-self and nonself-antigens CD1, CD5, CD19, CD20, CD22, CD27, CD9, CD11b, CD43, B220 CD1 (less common) (i) Natural antibody production (ii) Immunity against infection (iii) Pathogenesis of autoimmune disorders and CLL (i) IgM production (ii) IgG3 production (less common) (iii) IgA production in gut [21 –28 ]