Distinct migration patterns of naive and effector CD8 T cells in the spleen: correlation with CCR7 receptor expression and chemokine reactivity.
Changes in the migration pattern of lymphocytes represent a key event in the evolution of an immune response since they enable lymphocytes to gain access to infected tissues. We studied the location of virus-specific CD8 T cells in various splenic compartments in response to infection with lymphocytic choriomeningitis virus (LCMV), either in situ or by adoptive cell transfers using T cells from transgenic (tg) mice expressing an LCMV-specific TCR. Naive tg T cells were predominantly localized in the periarteriolar lymphoid sheath, where they proliferated extensively after virus infection. In contrast, in vivo activated effector T cells failed to enter white pulp areas and accumulated in the red pulp. The different homing patterns of naive and effector CD8 T cells in vivo correlated well with their CCR7 chemokine receptor expression and their reactivity to the secondary lymphoid tissue chemokine (SLC). Thus, down-regulation of CCR7 expression on CD8 effector T cells rendered them unre sponsive to SLC, which controls T cell homing into white pulp of spleen and lymph nodes. Exclusion of CD8 effector T cells from these sites may represent an important mechanism to protect professional antigen-presenting cells from cytotoxic T cell attack and thus to prevent a prematuredecline of the immune response.
Potsch
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Institute of Medical Microbiology, Department of Immunology, University of Freiburg, Freiburg, Germany.
Vöhringer
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Pircher
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D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000276:immunology; D002633:Chemotaxis / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine