Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivo.
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.
Tarazona
R
R
Division of Molecular Immunology, National Institute for Medcial Research, London, UK.
Sponaas
A M
AM
Mavria
G
G
Zhou
M
M
Schulz
R
R
Tomlinson
P
P
Antoniou
J
J
Mellor
A L
AL
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
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