Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivo |
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Authors: | Tarazona Requel; Sponaas Anna-Marit; Mavria Georgia; Zhou Mln; Schulz Ruth; Tomilnson Peter; Antoniou Jane; Mellor Andrew L |
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Institution: | Division of Molecular Immunology, National Institute for Medical Research The Ridgeway, Mill Hill, London NW7 1AA, UK
1 Immunogenetics Department, Institute of Molecular Medicine and Genetics, Medical College of Georgia 1120, 15th Street, Augusta, GA 30912-3175, USA |
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Abstract: | The influence of microenvironment on the course of CD8+ T cellresponses in vivo was investigated by injecting H-2Kb-specificT cells from donor TCR transgenlc (TCR-Tg) mice into H-2Kb-tagmice. H-2Kb expression in recipients was either ubiquitous (CBKmice) or restricted to myeloid and erythroid cells (Kßmice). Donor T cells proliferated as extensively and acquiredsimilar surface phenotypes in spleen of both recipient types.Thus, neither the restricted pattern of H-2Kb expression northe significantly reduced level of H-2Kb expression by myeloldcells in Kß recipients affects the ability of thesplenic microenvironment to prime T cell proliferation in vivo.However, an unsustained burst of cytolytic activity was generatedrapidly in spleen of CBK recipients, whereas relatively littlecytolytic activity was generated in Kß spleen. Thisindicates that effector T cells were not generated efficientlyin spleen of Kß recipients even though extensive Tcell proliferation was taking place in this microenvironment.Furthermore, activated donor T cells dispersed rapidly throughoutprimary and secondary lymphoid organs of Kß recipients,whereas few T cells migrated from spleen in CBK recipients.Consequently, the course of CD8+ T cell responses and the anatomicaldistribution of activated T cells are profoundly influencedby the nature of the antigenlc microenvironment encounteredin vivo. We conclude that T cells rapidly proliferate and acquirenew tissue-homing characteristics but do not differentiate intocytolytic effector cells at the site of priming when they encountermyelold cells expressing low levels of antigen in vivo. |
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Keywords: | activation cytotoxicity differentiation proliferation |
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