Table 1: Innate-like lymphocytes (ILLs) family.

Cell typeDate of discovery
and naming in the first publish
Main development
location
Major transcription
factors and molecules
needed for development
Anatomical locationsDevelopmental stage
that derived from
common progenitor
Major cytokines
produced by cells
Major stimulating
cytokines
Activator
and proliferator cells
Antigen
receptor
LigandsMajor
surface markers
MHC/MHC-like restrictionMajor functions and pathologyAntimicrobial defense mechanismsReference

MAIT (i) Porcelli et al. 1993 [3]  
(ii) Tilloy et al. 1999 [4]
ThymusPLZF (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 moleculesIL-12R, IL-18R, IL-23R
CD4CD8, 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)
[36]

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 nodesDouble positive (DP) (pro-T)IL-4
IL-10
IL-13
IFN-   
TGF-
IL-7
IL-12
IL-25
IL-33
TSLP
APCsTCR /   
V 14 (mouse)
V 24 (human)
Glycolipids especially -Gal-CerDN 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, 710]

/ T cell(i) Saito et al. 1984 [11]
(ii) Samelson et al. 1985 [12]
ThymusSox13
Id3
Egr-1
(i) Epiderm
(ii) Mucosal tissues
(iii) Blood (few numbers)
DN2IL-17
IFN-   
TNF-
IL-2
IL-7
IL-21
(i) Mostly by antigens directly
(ii) APCs (less common)
TCR
/
Mostly nonpeptidic-self and nonself-antigensNKRs: 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)
[1116]

MZBMacLennan 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 antigensCD1, 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[1720]

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-antigensCD1, 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
[2128]

MAIT: mucosal-associated invariant T cells, iNKT: invariant natural killer T cells, MZB: marginal zone B cells, MR1: MHC-related protein-1, Egr: early growth response, Id3: inhibitor of DNA binding-3, BAFF: B cell activation factor of the TNF family, Pyk: protein tyrosine kinase, Notch2: neurogenic locus notch homology protein 2, NFATc1: nuclear factor of activated T cell, cytoplasmic-1, S1P1: sphingosine-1-phosphate receptor-1, Sox: sex-determining region-(sry-) related high-mobility-group (HMG) box, PLZF: promyelocytic leukemia zinc finger, α-Gal-Cer: alpha-galactosylceramide, SLAM: signaling lymphocytic activation molecule, CLL: chronic lymphocytic leukemia.