Crossref journal-article
American Society of Hematology
Blood (234)
Abstract

AbstractMouse spleen contains CD4+, CD8α+, and CD4−/CD8α− dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule–associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8α+ DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC subtypes stimulated allogeneic CD4+ T cells comparably. However, CD8α+ DCs were very weak stimulators of resting or activated allogeneic CD8+ T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8+ F5 T-cell receptor (TCR)–transgenic T cells. CD8α− or CD8α+DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I–peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8α DCs was responsible for the low allostimulatory capacity of CD8α+ DCs in vitro. Surprisingly, both CD8α+ DCs and CD4−/CD8− DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4+ DCs were weak inducers of CTLs. Thus, the inability of CD8α+ DCs to stimulate CD8+ T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo interaction between CD8α+ DCs and CD8+ T cells.

Bibliography

McLellan, A. D., Kapp, M., Eggert, A., Linden, C., Bommhardt, U., Bröcker, E.-B., Kämmerer, U., & Kämpgen, E. (2002). Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression. Blood, 99(6), 2084–2093.

Authors 8
  1. Alexander D. McLellan (first)
  2. Michaela Kapp (additional)
  3. Andreas Eggert (additional)
  4. Christian Linden (additional)
  5. Ursula Bommhardt (additional)
  6. Eva-B. Bröcker (additional)
  7. Ulrike Kämmerer (additional)
  8. Eckhart Kämpgen (additional)
References 55 Referenced 112
  1. 10.4049/jimmunol.165.11.6037 / J Immunol. / BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. by Dzionek (2000)
  2. 10.4049/jimmunol.151.11.6535 / J Immunol. / Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets [published erratum appears in J Immunol 1994 Jan 1;152(1):376]. by Nestle (1993)
  3. 10.1084/jem.176.1.47 / J Exp Med. / The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells. by Vremec (1992)
  4. 10.1084/jem.178.3.1067 / J Exp Med. / Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium. by O'Doherty (1993)
  5. 10.4049/jimmunol.155.1.93 / J Immunol. / Antigen processing in populations of mature murine dendritic cells is caused by subsets of incompletely matured cells. by Koch (1995)
  6. 10.1046/j.1523-1747.1998.00375.x / J Invest Dermatol. / Dermal dendritic cells associated with T lymphocytes in normal human skin display an activated phenotype. by McLellan (1998)
  7. 10.4049/jimmunol.165.9.4910 / J Immunol. / Anatomical origin of dendritic cells determines their life span in peripheral lymph nodes. by Ruedl (2000)
  8. 10.1182/blood.V97.6.1733 / Blood. / Human thymus contains 2 distinct dendritic cell populations. by Vandenabeele (2001)
  9. 10.1182/blood.V89.10.3708 / Blood. / Isolation of human blood dendritic cells using the CMRF-44 monoclonal antibody: implications for studies on antigen-presenting cell function and immunotherapy. by Fearnley (1997)
  10. 10.1073/pnas.94.23.12551 / Proc Natl Acad Sci U S A. / Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin. by Olweus (1997)
  11. 10.1084/jem.185.6.1101 / J Exp Med. / The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. by Grouard (1997)
  12. 10.4049/jimmunol.163.6.3250 / J Immunol. / Survival, maturation, and function of CD11c- and CD11c+ peripheral blood dendritic cells are differentially regulated by cytokines. by Kohrgruber (1999)
  13. 10.1002/(SICI)1521-4141(199909)29:09<2769::AID-IMMU2769>3.0.CO;2-2 / Eur J Immunol. / Human peripheral blood contains two distinct lineages of dendritic cells. by Robinson (1999)
  14. 10.1046/j.1365-3083.1996.d01-289.x / Scand J Immunol. / The cell surface phenotype of human natural interferon-alpha producing cells as determined by flow cytometry. by Svensson (1996)
  15. 10.1038/11360 / Nat Med. / Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. by Cella (1999)
  16. 10.1084/jem.171.5.1753 / J Exp Med. / The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. by Metlay (1990)
  17. 10.4049/jimmunol.160.2.708 / J Immunol. / Three populations of mouse lymph node dendritic cells with different origins and dynamics. by Salomon (1998)
  18. 10.4049/jimmunol.164.6.2978 / J Immunol. / CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. by Vremec (2000)
  19. 10.1016/S0165-2478(00)00167-X / Immunol Lett. / Functions of myeloid and lymphoid dendritic cells. by McLellan (2000)
  20. 10.1084/jem.183.4.1789 / J Exp Med. / A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis. by Suss (1996)
  21. 10.4049/jimmunol.157.9.3819 / J Immunol. / A subclass of dendritic cells regulates the response of naive CD8 T cells by limiting their IL-2 production. by Kronin (1996)
  22. 10.1002/(SICI)1521-4141(199911)29:11<3762::AID-IMMU3762>3.0.CO;2-F / Eur J Immunol. / CTL priming by CD8(+) and CD8(-) dendritic cells in vivo. by Ruedl (1999)
  23. 10.1084/jem.192.12.1685 / J Exp Med. / CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo. by den Haan (2000)
  24. 10.4049/jimmunol.166.9.5327 / J Immunol. / Cutting edge: intravenous soluble antigen is presented to cd4 t cells by cd8(-) dendritic cells, but cross-presented to cd8 t cells by cd8(+) dendritic cells. by Pooley (2001)
  25. 10.1084/jem.186.11.1819 / J Exp Med. / In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas [see comments]. by Sousa (1997)
  26. 10.1084/jem.189.3.587 / J Exp Med. / CD8alpha+ and CD8alpha− subclasses of dendritic cells direct the development of distinct T helper cells in vivo. by Maldonado-Lopez (1999)
  27. 10.1084/jem.189.3.593 / J Exp Med. / Antigen-pulsed CD8alpha+ dendritic cells generate an immune response after subcutaneous injection without homing to the draining lymph node. by Smith (1999)
  28. 10.1016/0022-1759(90)90318-P / J Immunol Methods. / Use of the fluorescence activated cell sorter to enrich dendritic cells from mouse spleen. by Crowley (1990)
  29. 10.4049/jimmunol.165.12.6762 / J Immunol. / The development, maturation, and turnover rate of mouse spleen dendritic cell populations. by Kamath (2000)
  30. 10.4049/jimmunol.166.9.5448 / J Immunol. / Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets. by Hochrein (2001)
  31. 10.1073/pnas.89.23.11342 / Proc Natl Acad Sci U S A. / Thymic depletion and peripheral activation of class I major histocompatibility complex-restricted T cells by soluble peptide in T-cell receptor transgenic mice. by Mamalaki (1992)
  32. 10.1084/jem.180.6.2089 / J Exp Med. / Mechanisms of tolerance induction in major histocompatibility complex class II-restricted T cells specific for a blood-borne self-antigen. by Zal (1994)
  33. 10.1016/0022-1759(91)90325-A / J Immunol Methods / The JAM test. A simple assay for DNA fragmentation and cell death. by Matzinger (1991)
  34. 10.1046/j.1365-2567.1999.00860.x / Immunology. / Induction of dendritic cell costimulator molecule expression is suppressed by T cells in the absence of antigen-specific signaling: role of cluster formation, CD40 and HLA-class II for dendritic cell activation. by McLellan (1999)
  35. 10.1016/S1074-7613(00)80447-1 / Immunity. / Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. by Porgador (1997)
  36. 10.1016/S1074-7613(00)80160-0 / Immunity. / Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. by Valladeau (2000)
  37. 10.1002/jlb.67.5.622 / J Leukoc Biol. / Migration of dendritic cells within 3-D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines. by Gunzer (2000)
  38. 10.1182/blood.V93.3.952 / Blood. / Shaping the repertoire of cytotoxic T-lymphocyte responses: explanation for the immunodominance effect whereby cytotoxic T lymphocytes specific for immunodominant antigens prevent recognition of nondominant antigens. by Pion (1999)
  39. 10.1016/S1074-7613(00)80138-7 / Immunity. / Paralysis of dendritic cell IL-12 production by microbial products prevents infection-induced immunopathology. by Sousa (1999)
  40. 10.1084/jem.189.12.1981 / J Exp Med. / Interleukin 12-dependent interferon gamma production by CD8alpha+ lymphoid dendritic cells. by Ohteki (1999)
  41. 10.1016/S0955-0674(00)00132-0 / Curr Opin Cell Biol. / T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines. by Agace (2000)
  42. 10.1084/jem.191.3.435 / J Exp Med. / A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. by Huang (2000)
  43. 10.1093/intimm/12.5.731 / Int Immunol. / DEC-205 as a marker of dendritic cells with regulatory effects on CD8 T cell responses. by Kronin (2000)
  44. 10.1016/S1074-7613(00)80635-4 / Immunity. / Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8alphaalpha ectodomain fragment in complex with H-2Kb. by Kern (1998)
  45. 10.4049/jimmunol.162.11.6552 / J Immunol. / Analysis of adjuvant function by direct visualization of antigen presentation in vivo: endotoxin promotes accumulation of antigen-bearing dendritic cells in the T cell areas of lymphoid tissue. by Sousa (1999)
  46. 10.1084/jem.185.2.317 / J Exp Med. / Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. by Winzler (1997)
  47. 10.1002/(SICI)1521-4141(199910)29:10<3216::AID-IMMU3216>3.0.CO;2-X / Eur J Immunol. / Anti-CD40 antibody enhances responses to polysaccharide without mimicking T cell help. by Garcia (1999)
  48. 10.1038/362761a0 / Nature. / Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. by Ardavin (1993)
  49. 10.1073/pnas.96.26.15068 / Proc Natl Acad Sci U S A. / Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice. by Rodewald (1999)
  50. 10.1182/blood.V96.7.2511 / Blood. / Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8alpha(-) and CD8alpha(+) dendritic cells are generated from CD4(low) lymphoid-committed precursors. by Martin (2000)
  51. 10.1126/science.290.5499.2152 / Science. / Development of CD8alpha-positive dendritic cells from a common myeloid progenitor. by Traver (2000)
  52. 10.1182/blood.V97.11.3333 / Blood. / Dendritic cell potentials of early lymphoid and myeloid progenitors. by Manz (2001)
  53. 10.1016/S0022-1759(96)00117-2 / J Immunol Methods. / A method to recover, enumerate and identify lymphomyeloid cells present in an inflammatory dermal site: a study in laboratory mice. by Belkaid (1996)
  54. 10.1182/blood.V96.5.1865 / Blood. / Differentiation of myeloid dendritic cells into CD8alpha-positive dendritic cells in vivo. by Merad (2000)
  55. 10.1182/blood.V93.2.590 / Blood. / Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes, and skin of the mouse. by Anjuere (1999)
Dates
Type When
Created 22 years, 10 months ago (Oct. 1, 2002, 5:48 p.m.)
Deposited 2 years, 4 months ago (April 24, 2023, 3:37 p.m.)
Indexed 2 weeks ago (Aug. 12, 2025, 6:04 p.m.)
Issued 23 years, 5 months ago (March 15, 2002)
Published 23 years, 5 months ago (March 15, 2002)
Published Print 23 years, 5 months ago (March 15, 2002)
Funders 0

None

@article{McLellan_2002, title={Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression}, volume={99}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v99.6.2084}, DOI={10.1182/blood.v99.6.2084}, number={6}, journal={Blood}, publisher={American Society of Hematology}, author={McLellan, Alexander D. and Kapp, Michaela and Eggert, Andreas and Linden, Christian and Bommhardt, Ursula and Bröcker, Eva-B. and Kämmerer, Ulrike and Kämpgen, Eckhart}, year={2002}, month=mar, pages={2084–2093} }