title: Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivo.
abstract: The influence of microenvironment on the course of CD8 + T cell responses in vivo was investigated by injecting H-2Kb-specific T cells from donor TCR transgenic (TCR-Tg) mice into H-2kb-Tg mice. H-2Kb expression in recipients was either ubiquitous (CBK mice) or restricted to myeloid and erythroid cells (K beta mice). Donor T cells proliferated as extensively and acquired similar surface phenotypes in spleen of both recipient types. Thus, neither the restricted pattern of H-2Kb expression nor the significantly reduced level of H-2Kb expression by myeloid cells in Kbeta recipients affects the ability of the splenic microenvironment to prime T cell proliferation in vivo. However, an unsustained burst of cytolytic activity was generated rapidly in spleen of CBK recipients, whereas relatively little cytolytic activity was generated in K beta spleen. This indicates that effector T cells were not generated efficiently in spleen of Kbeta recipients even though extensive T cell proliferation was taking place in this microenvironment. Furthermore, activated donor T cells dispersed rapidly throughout primary and secondary lymphoid organs of Kbeta recipients, whereas few T cells migrated from spleen in CBK recipients. Consequently, the course of CD8+ T cell responses and the anatomical distribution of activated T cells are profoundly influenced by the nature of the antigenic microenvironment encountered in vivo. We conclude that T cells rapidly proliferate and acquire new tissue-homing characteristics but do not differentiate into cytolytic effector cells at the site of priming when they encounter myeloid cells expressing low levels of antigen in vivo.
authors.affiliation: Division of Molecular Immunology, National Institute for Medcial Research, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Tarazona
authors.forename: A M
authors.initials: AM
authors.lastname: Sponaas
authors.forename: G
authors.initials: G
authors.lastname: Mavria
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.forename: R
authors.initials: R
authors.lastname: Schulz
authors.forename: P
authors.initials: P
authors.lastname: Tomlinson
authors.forename: J
authors.initials: J
authors.lastname: Antoniou
authors.forename: A L
authors.initials: AL
authors.lastname: Mellor
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D019087:Selectins / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D014018:Tissue Distribution
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D018960:Hyaluronan Receptors; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2; D019087:Selectins