Secondary Lymphoid Tissue Cells Maintain Memory CD4 T Cells within Cutting Edge: Lymphoid Tissue Inducer

Phylogeny shows that CD4 T cell memory and lymph nodes coevolved in placental mammals. In ontogeny, retinoic acid orphan receptor (ROR) g -dependent lymphoid tissue inducer (LTi) cells program the develop-ment of mammalian lymph nodes. In this study, we show that although primary CD4 T cell expansion is normal in ROR g -deficient mice, the persistence of memory CD4 T cells is ROR g -dependent. Further-more, using bone marrow chimeric mice we demonstrate that LTi cells are the key ROR g -expressing cell type sufficient for memory CD4 T cell survival in the absence of persistent Ag. This effect was specific for CD4 T cells, as memory CD8 T cells survived equally well in the presence or absence of LTi cells. These data demonstrate a novel role for LTi cells, archetypal members of the innate lymphoid cell family, in supporting memory CD4 T cell survival in vivo. The Journal of Immunology , 2012, 189: 000–000.

[1]  G. Anderson,et al.  OX40 and CD30 signals in CD4+ T‐cell effector and memory function: a distinct role for lymphoid tissue inducer cells in maintaining CD4+ T‐cell memory but not effector function , 2011, Immunological reviews.

[2]  M. Jenkins,et al.  Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. , 2011, Immunity.

[3]  S. Halle,et al.  Afferent lymph–derived T cells and DCs use different chemokine receptor CCR7–dependent routes for entry into the lymph node and intranodal migration , 2011, Nature Immunology.

[4]  G. Anderson,et al.  Abrogation of CD30 and OX40 signals prevents autoimmune disease in FoxP3-deficient mice , 2011, The Journal of experimental medicine.

[5]  G. Anderson,et al.  CD117+CD3−CD56−OX40Lhigh cells express IL‐22 and display an LTi phenotype in human secondary lymphoid tissues , 2011, European journal of immunology.

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

[7]  Jonathan L. Linehan,et al.  Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH-17 cells , 2009, Nature Immunology.

[8]  A. Kreiss,et al.  The humoral immune response of the Tasmanian devil (Sarcophilus harrisii) against horse red blood cells. , 2009, Veterinary immunology and immunopathology.

[9]  S. Hemsley,et al.  A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil , 2009, Anatomical record.

[10]  M. Bedford,et al.  IL7‐hCD25 and IL7‐Cre BAC transgenic mouse lines: New tools for analysis of IL‐7 expressing cells , 2009, Genesis.

[11]  C. Tato,et al.  Lymphoid tissue inducer–like cells are an innate source of IL-17 and IL-22 , 2009, The Journal of experimental medicine.

[12]  Andreas Diefenbach,et al.  RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22–producing NKp46+ cells , 2009, Nature Immunology.

[13]  Shinichiro Sawa,et al.  Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. , 2008, Immunity.

[14]  J. Sprent,et al.  Homeostasis of naive and memory T cells. , 2008, Immunity.

[15]  Ronald N. Germain,et al.  Fibroblastic Reticular Cells Guide T Lymphocyte Entry into and Migration within the Splenic T Cell Zone1 , 2008, The Journal of Immunology.

[16]  Keiichiro Suzuki,et al.  Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. , 2008, Immunity.

[17]  T. Junt,et al.  Restoration of lymphoid organ integrity through the interaction of lymphoid tissue–inducer cells with stroma of the T cell zone , 2008, Nature Immunology.

[18]  I. Mårtensson,et al.  OX40 Ligand and CD30 Ligand Are Expressed on Adult but Not Neonatal CD4+CD3− Inducer Cells: Evidence That IL-7 Signals Regulate CD30 Ligand but Not OX40 Ligand Expression1 , 2005, The Journal of Immunology.

[19]  P. Lane,et al.  Mice Deficient in OX40 and CD30 Signals Lack Memory Antibody Responses because of Deficient CD4 T Cell Memory1 , 2005, The Journal of Immunology.

[20]  P. Lane,et al.  Mice Deficient in OX 40 and CD 30 Signals , 2005 .

[21]  B. Munday,et al.  Antibody response to sheep red blood cells in platypus and echidna. , 2003, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[22]  P. Lane,et al.  CD4(+)CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. , 2003, Immunity.

[23]  S. Hemsley,et al.  The roles of histology and immunohistology in the investigation of marsupial disease and normal lymphoid tissue. , 2000, Developmental and comparative immunology.

[24]  A. Pierani,et al.  Requirement for RORgamma in thymocyte survival and lymphoid organ development. , 2000, Science.

[25]  E. Lacy,et al.  A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Kristin A. Hogquist,et al.  T cell receptor antagonist peptides induce positive selection , 1994, Cell.

[27]  Susumu Tonegawa,et al.  RAG-1-deficient mice have no mature B and T lymphocytes , 1992, Cell.

[28]  E. Diener,et al.  Immune System in a Monotreme: Studies on the Australian Echidna (Tachyglossus aculeatus) , 1965, Nature.