Ontogeny of Innate T Lymphocytes – Some Innate Lymphocytes are More Innate than Others

Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is “innate” in lymphocytes. Lymphocytes without V(D)J-rearranged antigen receptors are now termed innate lymphoid cells (ILCs) and include cells formerly known as natural killer (NK) cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, genuine innate lymphocytes would be present before or at birth. Here, we review the ontogeny of human and mouse innate T lymphocyte populations. We focus on γδ T cells, which are prototype lymphocytes that often use their V(D)J rearrangement machinery to generate genetically encoded predetermined recombinations of antigen receptors. We make parallels between the development of γδ T cells with that of innate αβ T cells [invariant (i)NKT and mucosa-associated invariant T cells] and compare this with the ontogeny of innate B cells and ILCs (including NK cells). We conclude that some subsets are more innate than others, i.e., innate lymphocytes that are made primarily early in utero during gestation while others are made after birth. In practice, a ranking of innateness by ontogeny has implications for the reconstitution of innate lymphocyte subsets after hematopoietic stem cell transplantation.

[1]  A. Ross,et al.  α‐Galactosylceramide stimulates splenic lymphocyte proliferation in vitro and increases antibody production in vivo in late neonatal‐age mice , 2015, Clinical and experimental immunology.

[2]  D. Olive,et al.  Vγ9Vδ2 TCR‐activation by phosphorylated antigens requires butyrophilin 3 A1 (BTN3A1) and additional genes on human chromosome 6 , 2014, European journal of immunology.

[3]  E. Pamer,et al.  Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens , 2014, The Journal of experimental medicine.

[4]  Gabrielle T. Belz,et al.  Nfil3 is required for the development of all innate lymphoid cell subsets , 2014, The Journal of experimental medicine.

[5]  F. Rödel,et al.  Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. , 2014, Biochimica et biophysica acta.

[6]  B. Blom,et al.  Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. , 2014, Blood.

[7]  G. Trinchieri Critical role for CX3CR1+ mononuclear phagocytes in intestinal homeostasis , 2014, The Journal of experimental medicine.

[8]  Joseph C. Sun,et al.  Proapoptotic Bim regulates antigen-specific NK cell contraction and the generation of the memory NK cell pool after cytomegalovirus infection , 2014, The Journal of experimental medicine.

[9]  Huang-Ge Zhang,et al.  Differential Developmental Requirement and Peripheral Regulation for Dermal Vγ4 and Vγ6T17 Cells in Health and Inflammation , 2014, Nature Communications.

[10]  F. Ginhoux,et al.  Monocytes and macrophages: developmental pathways and tissue homeostasis , 2014, Nature Reviews Immunology.

[11]  E. Newell,et al.  Correction: Corrigendum: Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire , 2014, Nature Communications.

[12]  V. Colizzi,et al.  Cord blood Vγ2Vδ2 T cells provide a molecular marker for the influence of pregnancy-associated malaria on neonatal immunity. , 2014, The Journal of infectious diseases.

[13]  James E. Crooks,et al.  The intracellular B30.2 domain of butyrophilin 3A1 binds phosphoantigens to mediate activation of human Vγ9Vδ2 T cells. , 2014, Immunity.

[14]  Henrique Veiga-Fernandes,et al.  Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages , 2014, Cell.

[15]  D. Sinderen,et al.  T-cell activation by transitory neo-antigens derived from distinct microbial pathways , 2014, Nature.

[16]  D. Nixon,et al.  Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine , 2014, Mucosal Immunology.

[17]  L. Walter,et al.  Vγ9 and Vδ2 T cell antigen receptor genes and butyrophilin 3 (BTN3) emerged with placental mammals and are concomitantly preserved in selected species like alpaca (Vicugna pacos) , 2014, Immunogenetics.

[18]  D. Nixon,et al.  Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development , 2014, Nature Communications.

[19]  E. Adams,et al.  Crystal Structure of V delta 1 T Cell Receptor in Complex with CD1d-Sulfatide Shows MHC-like Recognition of a Self-Lipid by Human gamma delta T Cells. , 2013 .

[20]  O. Lantz,et al.  Double Positive Thymocytes Select Mucosal-Associated Invariant T Cells , 2013, The Journal of Immunology.

[21]  F. Locatelli,et al.  Impact of HCMV Infection on NK Cell Development and Function after HSCT , 2013, Front. Immunol..

[22]  Damien Picard,et al.  Crystal structure of Vδ1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human γδ T cells. , 2013, Immunity.

[23]  P. Vantourout,et al.  A long-playing CD about the γδ TCR repertoire. , 2013, Immunity.

[24]  B. L. Anderson,et al.  Stimulation of Natural Killer T Cells by Glycolipids , 2013, Molecules.

[25]  A. Hayday,et al.  Innate-like T cells straddle innate and adaptive immunity by revising antigen-receptor responsiveness , 2013, Nature Immunology.

[26]  S. Jameson,et al.  Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells , 2013, Nature Immunology.

[27]  Jamie Rossjohn,et al.  CD1d-lipid antigen recognition by the γδ TCR , 2013, Nature Immunology.

[28]  D. Nixon,et al.  Differentiation and functional regulation of human fetal NK cells. , 2013, The Journal of clinical investigation.

[29]  Sabyasachi Das,et al.  Evolutionary implications of a third lymphocyte lineage in lampreys , 2013, Nature.

[30]  D. Pennington,et al.  Functional development of γδ T cells , 2013, European journal of immunology.

[31]  M. Distefano,et al.  Butyrophilin 3A1 Plays an Essential Role in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells , 2013, The Journal of Immunology.

[32]  Han-Hsuan Fu,et al.  γδ T cells exhibit multifunctional and protective memory in intestinal tissues. , 2013, Immunity.

[33]  N. K. Williams,et al.  Butyrophilin 3A1 binds phosphorylated antigens and stimulates human γδ T cells , 2013, Nature Immunology.

[34]  F. Schuit,et al.  Characterization of proposed human B-1 cells reveals pre-plasmablast phenotype. , 2013, Blood.

[35]  S. Tangye To B1 or not to B1: that really is still the question! , 2013, Blood.

[36]  B. Vandekerckhove,et al.  Abundant stage‐dependent Ly49E expression by liver NK cells is not essential for their differentiation and function , 2013, Journal of leukocyte biology.

[37]  M. Ballmaier,et al.  Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells , 2013, Proceedings of the National Academy of Sciences.

[38]  L. Harrison,et al.  Ex‐vivo analysis of human Natural Killer T cells demonstrates heterogeneity between tissues and within established CD4+ and CD4− subsets , 2013, Clinical and experimental immunology.

[39]  Y. Chien,et al.  The natural and the inducible: interleukin (IL)-17-producing γδ T cells. , 2013, Trends in immunology.

[40]  Irene Puga,et al.  Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes , 2013, Nature Reviews Immunology.

[41]  P. Vantourout,et al.  Six-of-the-best: unique contributions of γδ T cells to immunology , 2013, Nature Reviews Immunology.

[42]  Eric Vivier,et al.  Innate lymphoid cells — a proposal for uniform nomenclature , 2013, Nature Reviews Immunology.

[43]  M. Eberl,et al.  γδ T‐cell conference 2012: Close encounters for the fifth time , 2012, European journal of immunology.

[44]  M. Perales,et al.  Immune recovery after allogeneic hematopoietic stem cell transplantation: is it time to revisit how patients are monitored? , 2012, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[45]  D. Kabelitz,et al.  Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic , 2012, Cellular and Molecular Immunology.

[46]  Mark M. Davis,et al.  γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen-specific interleukin-17 response. , 2012, Immunity.

[47]  M. Cavazzana‐Calvo,et al.  Early posttransplantation donor-derived invariant natural killer T-cell recovery predicts the occurrence of acute graft-versus-host disease and overall survival. , 2012, Blood.

[48]  R. Jenq,et al.  Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. , 2012, Immunity.

[49]  Carrie R Willcox,et al.  Cytomegalovirus and tumor stress surveillance by binding of a human γδ T cell antigen receptor to endothelial protein C receptor , 2012, Nature Immunology.

[50]  A. Krueger,et al.  Development of interleukin-17-producing γδ T cells is restricted to a functional embryonic wave. , 2012, Immunity.

[51]  D. Pennington,et al.  Understanding the complexity of γδ T‐cell subsets in mouse and human , 2012, Immunology.

[52]  P. Streeter,et al.  Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress , 2012, Mucosal Immunology.

[53]  S. Sansano,et al.  Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus , 2012, Nature Immunology.

[54]  E. Montecino-Rodriguez,et al.  B-1 B cell development in the fetus and adult. , 2012, Immunity.

[55]  G. Besra,et al.  Invariant natural killer T cells recognize lipid self-antigen induced by microbial danger signals , 2011, Nature Immunology.

[56]  Lewis L. Lanier,et al.  NK cell development, homeostasis and function: parallels with CD8+ T cells , 2011, Nature Reviews Immunology.

[57]  E. Montecino-Rodriguez,et al.  Reduced production of B-1–specified common lymphoid progenitors results in diminished potential of adult marrow to generate B-1 cells , 2011, Proceedings of the National Academy of Sciences.

[58]  A. Hayday,et al.  Skint-1 identifies a common molecular mechanism for the development of interferon-γ-secreting versus interleukin-17-secreting γδ T cells. , 2011, Immunity.

[59]  C. Desmarais,et al.  Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment , 2011, Science Translational Medicine.

[60]  Elizabeth E Gray,et al.  Cutting Edge: Identification of a Motile IL-17–Producing γδ T Cell Population in the Dermis , 2011, The Journal of Immunology.

[61]  M. Goldman,et al.  IL‐23R and TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells expressing high levels of cytotoxic mediators and producing IFN‐γ and IL‐17 , 2011, Journal of leukocyte biology.

[62]  L. Sangalli,et al.  Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4− Subset Dynamics and Correlates with Remission State , 2011, The Journal of Immunology.

[63]  L. Ng,et al.  Cutaneous immunosurveillance by self-renewing dermal γδ T cells , 2011, The Journal of experimental medicine.

[64]  T. Rothstein,et al.  Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+CD27+CD43+CD70− , 2011, The Journal of experimental medicine.

[65]  M. Caligiuri,et al.  Innate or Adaptive Immunity? The Example of Natural Killer Cells , 2011, Science.

[66]  Jeff E. Mold,et al.  Fetal and Adult Hematopoietic Stem Cells Give Rise to Distinct T Cell Lineages in Humans , 2010, Science.

[67]  B. Malissen,et al.  Intra- and Intercompartmental Movement of γδ T Cells: Intestinal Intraepithelial and Peripheral γδ T Cells Represent Exclusive Nonoverlapping Populations with Distinct Migration Characteristics , 2010, The Journal of Immunology.

[68]  S. Grace,et al.  The role of Vδ2-negative γδ T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation. , 2010, Blood.

[69]  M. Bonneville,et al.  γδ T cell effector functions: a blend of innate programming and acquired plasticity , 2010, Nature Reviews Immunology.

[70]  P. Debré,et al.  Shaping of iNKT cell repertoire after unrelated cord blood transplantation. , 2010, Clinical immunology.

[71]  M. Goldman,et al.  Human cytomegalovirus elicits fetal γδ T cell responses in utero , 2010, The Journal of experimental medicine.

[72]  Tak W. Mak,et al.  Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo , 2009, The Journal of experimental medicine.

[73]  A. Waisman,et al.  Induction of B-cell development in adult mice reveals the ability of bone marrow to produce B-1a cells. , 2009, Blood.

[74]  E. Kremmer,et al.  CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells , 2009, European journal of immunology.

[75]  Mark Coles,et al.  The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development , 2009, Nature Immunology.

[76]  E. Adams,et al.  Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes , 2009, PLoS biology.

[77]  M. Veldhoen,et al.  Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. , 2009, Immunity.

[78]  O. Boyman,et al.  Cutting Edge: IL-7 Regulates the Peripheral Pool of Adult RORγ+ Lymphoid Tissue Inducer Cells1 , 2009, The Journal of Immunology.

[79]  C. Langford,et al.  Neonates harbour highly active γδ T cells with selective impairments in preterm infants , 2009, European journal of immunology.

[80]  D. Doherty,et al.  Invariant NKT cells and CD1d+ cells amass in human omentum and are depleted in patients with cancer and obesity , 2009, European journal of immunology.

[81]  Joseph C. Sun,et al.  Do the terms innate and adaptive immunity create conceptual barriers? , 2009, Nature Reviews Immunology.

[82]  O. Lantz,et al.  Stepwise Development of MAIT Cells in Mouse and Human , 2009, PLoS biology.

[83]  W. Born,et al.  IL‐17‐producing γδ T cells , 2009, European Journal of Immunology.

[84]  Joseph C. Sun,et al.  Adaptive Immune Features of Natural Killer Cells , 2009, Nature.

[85]  M. Suter,et al.  Phenotype and function of neonatal DC , 2009, European journal of immunology.

[86]  H. Spits,et al.  T cell–independent development and induction of somatic hypermutation in human IgM+IgD+CD27+ B cells , 2008, The Journal of experimental medicine.

[87]  S. Nakae,et al.  IL-17A Produced by γδ T Cells Plays a Critical Role in Innate Immunity against Listeria monocytogenes Infection in the Liver1 , 2008, The Journal of Immunology.

[88]  Mark M. Davis,et al.  Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. , 2008, Immunity.

[89]  D. Pellicci,et al.  Humans Lack iGb3 Due to the Absence of Functional iGb3-Synthase: Implications for NKT Cell Development and Transplantation , 2008, PLoS biology.

[90]  E. Brunetti,et al.  Vδ2 T‐lymphocyte responses in cord blood samples from Italy and Côte d’Ivoire , 2008, Immunology.

[91]  Eric Vivier,et al.  Functions of natural killer cells , 2008, Nature Immunology.

[92]  Julia M. Lewis,et al.  Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells , 2008, Nature Genetics.

[93]  D. Raulet,et al.  Gene placement and competition control T cell receptor γ variable region gene rearrangement , 2008, The Journal of experimental medicine.

[94]  C. Siegrist The challenges of vaccine responses in early life: selected examples. , 2007, Journal of comparative pathology.

[95]  B. Kee,et al.  Mature natural killer cell and lymphoid tissue–inducing cell development requires Id2-mediated suppression of E protein activity , 2007, The Journal of experimental medicine.

[96]  Albert Bendelac,et al.  The biology of NKT cells. , 2007, Annual review of immunology.

[97]  Y. Chien,et al.  Antigen recognition by γδ T cells , 2007 .

[98]  É. Vivier What is natural in natural killer cells? , 2006, Immunology letters.

[99]  D. Middleton,et al.  Human NK cell education by inhibitory receptors for MHC class I. , 2006, Immunity.

[100]  Julia M. Lewis,et al.  Selection of the cutaneous intraepithelial γδ+ T cell repertoire by a thymic stromal determinant , 2006, Nature Immunology.

[101]  U. V. Andrian,et al.  T cell– and B cell–independent adaptive immunity mediated by natural killer cells , 2006, Nature Immunology.

[102]  L. Lybarger,et al.  Licensing of natural killer cells by host major histocompatibility complex class I molecules , 2005, Nature.

[103]  D. Pellicci,et al.  Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples , 2005, European journal of immunology.

[104]  K. Christopher Garcia,et al.  Structure of a γδ T Cell Receptor in Complex with the Nonclassical MHC T22 , 2005, Science.

[105]  K. Weinberg,et al.  Distinct homeostatic requirements of CD4+ and CD4- subsets of Valpha24-invariant natural killer T cells in humans. , 2004, Blood.

[106]  R. Proia,et al.  Lysosomal Glycosphingolipid Recognition by NKT Cells , 2004, Science.

[107]  D. Nixon,et al.  Development of innate CD4+ α-chain variable gene segment 24 (Vα24) natural killer T cells in the early human fetal thymus is regulated by IL-7 , 2004 .

[108]  M. Roederer,et al.  Ontogeny of γδ T Cells in Humans , 2004, The Journal of Immunology.

[109]  P. Pereira,et al.  Most IL-4-Producing γδ Thymocytes of Adult Mice Originate from Fetal Precursors 1 , 2003, The Journal of Immunology.

[110]  J. Wiesner,et al.  Microbial isoprenoid biosynthesis and human γδ T cell activation , 2003, FEBS letters.

[111]  G. Leclercq,et al.  Ly49E expression points toward overlapping, but distinct, natural killer (NK) cell differentiation kinetics and potential of fetal versus adult lymphoid progenitors , 2003, Journal of leukocyte biology.

[112]  Olivier Lantz,et al.  Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1 , 2003, Nature.

[113]  G. Leclercq,et al.  Expression of Inhibitory Receptors Ly49E and CD94/NKG2 on Fetal Thymic and Adult Epidermal TCR Vγ3 Lymphocytes1 , 2002, The Journal of Immunology.

[114]  D. Pellicci,et al.  A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1−CD4+ CD1d-dependent Precursor Stage , 2002, The Journal of experimental medicine.

[115]  Marc Bonneville,et al.  Autoreactivity by design: innate B and T lymphocytes , 2001, Nature Reviews Immunology.

[116]  M. Kronenberg,et al.  NKT cells derive from double-positive thymocytes that are positively selected by CD1d , 2001, Nature Immunology.

[117]  G. Leclercq,et al.  Expression of Ly49E and CD94/NKG2 on Fetal and Adult NK Cells1 , 2001, The Journal of Immunology.

[118]  S. Beck,et al.  The cluster of BTN genes in the extended major histocompatibility complex. , 2001, Genomics.

[119]  A. Bendelac,et al.  Unaltered phenotype, tissue distribution and function of Vα14+ NKT cells in germ‐free mice , 2000, European journal of immunology.

[120]  P. Pereira,et al.  IL-4-producing gamma delta T cells that express a very restricted TCR repertoire are preferentially localized in liver and spleen. , 1999, Journal of immunology.

[121]  M. Bonneville,et al.  An Invariant T Cell Receptor α Chain Defines a Novel TAP-independent Major Histocompatibility Complex Class Ib–restricted α/β T Cell Subpopulation in Mammals , 1999, The Journal of experimental medicine.

[122]  Ahmed Mansouri,et al.  Development of peripheral lymphoid organs and natural killer cells depends on the helix–loop–helix inhibitor Id2 , 1999, Nature.

[123]  A. Hayday,et al.  The Generation of Human γδ T Cell Repertoires During Fetal Development , 1998, The Journal of Immunology.

[124]  I. Weissman,et al.  Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. , 1997, Immunity.

[125]  P. Pereira,et al.  A novel subset of adult γδ thymocytes that secretes a distinct pattern of cytokines and expresses a very restricted T cell receptor repertoire , 1997 .

[126]  S. Carding,et al.  Extrathymic origin of human gamma delta T cells during fetal development. , 1996, Journal of immunology.

[127]  T. Mak,et al.  Comparison of human and mouse T-cell receptor variable gene segment subfamilies , 1995, Immunogenetics.

[128]  W. Leonard,et al.  Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. , 1995, Immunity.

[129]  H. Band,et al.  TCR usage and functional capabilities of human gamma delta T cells at birth. , 1994, Journal of immunology.

[130]  M. Dessing,et al.  Homing and in situ differentiation of resident pulmonary lymphocytes. , 1994, International immunology.

[131]  M. Bonneville,et al.  Peripheral selection of antigen receptor junctional features in a major human γδ subset , 1993 .

[132]  A. Lanzavecchia,et al.  Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells , 1991, The Journal of experimental medicine.

[133]  A. Hayday,et al.  Regulated expression and structure of T cell receptor gamma/delta transcripts in human thymic ontogeny. , 1991, The EMBO journal.

[134]  I. Weissman,et al.  A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells , 1990, Cell.

[135]  J. Strominger,et al.  Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire , 1990, The Journal of experimental medicine.

[136]  S. Tonegawa,et al.  Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity , 1990, The Journal of experimental medicine.

[137]  S. Tonegawa,et al.  Homing of a γδ thymocyte subset with homogeneous T-cell receptors to mucosal epithelia , 1990, Nature.

[138]  J. Allison,et al.  Limited diversity of T-cell receptor gamma-chain expression of murine Thy-1+ dendritic epidermal cells revealed by V gamma 3-specific monoclonal antibody. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[139]  S. Tonegawa,et al.  T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. , 1989, Journal of immunology.

[140]  J. Allison,et al.  Limited diversity of γδ antigen receptor genes of thy-1+ dendritic epidermal cells , 1988, Cell.

[141]  P. Marrack,et al.  The T cell receptor. , 1987, Science.

[142]  J. Klein,et al.  Infectious Diseases of the Fetus and Newborn Infant , 1983 .

[143]  R. Kiessling,et al.  „Natural”︁ killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell , 1975, European journal of immunology.

[144]  R. Kiessling,et al.  „Natural”︁ killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype , 1975, European journal of immunology.

[145]  Selected Examples. , 1903 .

[146]  D. Baarle,et al.  γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia , 2013, Leukemia.

[147]  H. Spits,et al.  The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling , 2011, Nature Immunology.

[148]  D. Geffen Reduced production of B-1-specified common lymphoid progenitors results in diminished potential of adult marrow to generate B-1 cells , 2011 .

[149]  S. Nakae,et al.  IL-17A produced by gammadelta T cells plays a critical role in innate immunity against listeria monocytogenes infection in the liver. , 2008, Journal of immunology.

[150]  Y. Chien,et al.  Antigen recognition by gammadelta T cells. , 2007, Immunological reviews.

[151]  A. Hayday,et al.  Selection of the cutaneous intraepithelial gammadelta+ T cell repertoire by a thymic stromal determinant. , 2006, Nature immunology.

[152]  Christopher B Wilson,et al.  Developmental Immunology and Role of Host Defenses in Fetal and Neonatal Susceptibility to Infection , 2006 .

[153]  E. Adams,et al.  Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22. , 2005, Science.

[154]  D. Nixon,et al.  Development of innate CD4+ alpha-chain variable gene segment 24 (Valpha24) natural killer T cells in the early human fetal thymus is regulated by IL-7. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[155]  M. Roederer,et al.  Ontogeny of gamma delta T cells in humans. , 2004, Journal of immunology.

[156]  P. Pereira,et al.  Most IL-4-producing gamma delta thymocytes of adult mice originate from fetal precursors. , 2003, Journal of immunology.

[157]  S. Carding,et al.  Gammadelta T cells: functional plasticity and heterogeneity. , 2002, Nature reviews. Immunology.

[158]  A. Hayday [gamma][delta] cells: a right time and a right place for a conserved third way of protection. , 2000, Annual review of immunology.

[159]  A. Hayday,et al.  The generation of human gammadelta T cell repertoires during fetal development. , 1998, Journal of immunology.

[160]  P. Pereira,et al.  A novel subset of adult gamma delta thymocytes that secretes a distinct pattern of cytokines and expresses a very restricted T cell receptor repertoire. , 1997, European journal of immunology.

[161]  M. Bonneville,et al.  Peripheral selection of antigen receptor junctional features in a major human gamma delta subset. , 1993, European journal of immunology.

[162]  S. Tonegawa,et al.  Homing of a gamma delta thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. , 1990, Nature.

[163]  J. Allison,et al.  Limited diversity of gamma delta antigen receptor genes of Thy-1+ dendritic epidermal cells. , 1988, Cell.

[164]  Y. Shoenfeld,et al.  [The T cell receptor]. , 1985, Harefuah.

[165]  R. Kiessling NATURAL KILLER CELLS IN THE MOUSE , 1976 .