Role of CD 8 a 1 and CD 8 a 2 dendritic cells in the induction of primary immune responses in vivo

Data from adoptive transfer of mature dendritic cells (DC) indicate that they are responsible for the induction of primary immunity. Two subclasses of DC have been recently identified in spleen that differ in their phenotype and in certain regulatory features. In vitro, both subsets have the capacity to activate naive T cells, although CD8a1 DC have been shown to induce T cell apoptosis and to stimulate lower levels of cytokines compared with CD8a2 DC. The objective of this study was to analyze the function of these distinct DC types in vivo. Our results show that both subsets, pulsed extracorporeally with antigen and injected in the footpads of syngeneic mice, sensitize an antigenspecific T cell primary response. However, CD8a1 cells trigger the development of Th1-type cells, whereas CD8a2 DC induce a Th2-type response. These observations suggest that the Th1/Th2 balance in vivo is regulated by the antigen-presentingcells of the primary immune responses. J. Leukoc. Biol. 66: 242–246; 1999.

[1]  B. Pulendran,et al.  Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Adrian L. Smith,et al.  Antigen-pulsed CD8α+ Dendritic Cells Generate an Immune Response after Subcutaneous Injection without Homing to the Draining Lymph Node , 1999, The Journal of experimental medicine.

[3]  R. Maldonado-López,et al.  CD8α+ and CD8α− Subclasses of Dendritic Cells Direct the Development of Distinct T Helper Cells In Vivo , 1999, The Journal of experimental medicine.

[4]  A. D'amico,et al.  RelB Is Essential for the Development of Myeloid-Related CD8α− Dendritic Cells but Not of Lymphoid-Related CD8α+ Dendritic Cells , 1998 .

[5]  J. Bluestone,et al.  LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. , 1998, Journal of Immunology.

[6]  Fabrizio De Mattia,et al.  Regulation of T helper cell differentiation in vivo by soluble and membrane proteins provided by antigen‐presenting cells , 1998, European journal of immunology.

[7]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[8]  A. O’Garra,et al.  Cytokines induce the development of functionally heterogeneous T helper cell subsets. , 1998, Immunity.

[9]  A. Sher,et al.  In Vivo Microbial Stimulation Induces Rapid CD40 Ligand–independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas , 1997, The Journal of experimental medicine.

[10]  B. Pulendran,et al.  Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. , 1997, Journal of immunology.

[11]  K. Shortman,et al.  Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. , 1997, Journal of immunology.

[12]  E. Maraskovsky,et al.  Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified , 1996, The Journal of experimental medicine.

[13]  J. Bluestone,et al.  The Complexities of T‐Cell Co‐stimulation: CD28 and Beyond , 1996, Immunological reviews.

[14]  P. De Baetselier,et al.  Regulation of Dendritic Cell Numbers and Maturation by Lipopolysaccharide in Vivo , 1996 .

[15]  K. Shortman,et al.  Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny , 1996, The Journal of experimental medicine.

[16]  D. Carvajal,et al.  IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses , 1996 .

[17]  K. Shortman,et al.  A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand- induced apoptosis , 1996, The Journal of experimental medicine.

[18]  A. Woodard,et al.  Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells , 1995, The Journal of experimental medicine.

[19]  R. Seder Acquisition of lymphokine-producing phenotype by CD4+ T cells. , 1994, The Journal of allergy and clinical immunology.

[20]  M. Moser,et al.  Immunoglobulin isotype regulation by antigen‐presenting cells in vivo , 1994, European journal of immunology.

[21]  C. Hsieh,et al.  Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. , 1993, Science.

[22]  Li Wu,et al.  The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells , 1992, The Journal of experimental medicine.

[23]  R. Locksley,et al.  Reconstitution of Leishmania immunity in severe combined immunodeficient mice using Th1- and Th2-like cell lines. , 1991, Journal of immunology.

[24]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[25]  B. Fazekas de St. Groth,et al.  The evolution of self-tolerance: a new cell arises to meet the challenge of self-reactivity. , 1998, Immunology today.

[26]  Li Wu,et al.  Early T lymphocyte progenitors. , 1996, Annual review of immunology.

[27]  G. Trinchieri Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. , 1995, Annual review of immunology.

[28]  R. Coffman,et al.  Regulation of immunity to parasites by T cells and T cell-derived cytokines. , 1992, Annual review of immunology.

[29]  R. Coffman,et al.  TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. , 1989, Annual review of immunology.