Cutting edge: ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis.
To test whether accumulation of naive lymphocytes is sufficient to trigger lymphoid development, we generated mice with islet expression of the chemokine TCA4/SLC. This chemokine is specific for naive lymphocytes and mature dendritic cells (DC) which express the CCR7 receptor. Islets initially developed accumulations of T cells with DC, with scattered B cells at the perimeter. These infiltrates consolidated into organized lymphoid tissue, with high endothelial venules and stromal reticulum. Infiltrate lymphocytes showed a naive CD44low CD25- CD69- phenotype, though half were CD62L negative. When backcrossed to RAG-1 knockout, DC were not recruited. Interestingly, islet lymphoid tissue developed in backcrosses to Ikaros knockout mice despite the absence of normal peripheral nodes. Our results indicate that TCA4/SLC can induce the development and organization of lymphoid tissue through diffential recruitment of T and B lymphocytes and secondary effects on stromal cell development.
Fan
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Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Reilly
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CR
Luo
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Dorf
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Lo
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D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002465:Cell Movement / Q000276:immunology; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats
D015415:Biomarkers; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D007328:Insulin