Lymph node stromal cells strongly influence immune response suppression.
Many pathogens are initially encountered in the gut, where the decision is made to mount an immune response or induce tolerance. The mesentric lymph node (mLN) has been shown to be involved in immune response and much more in oral tolerance induction. Furthermore, using an in vivo transplantation model, we showed recently that lymph node (LN) stromal cells can affect T-cell function and influence the IgA response by supporting a site-specific environment. To elucidate the importance of LN stromal cells for tolerance induction, mLN or peripheral LN were transplanted into mice (mLNtx or pLNtx) and oral tolerance was induced via ovalbumin. A reduced delayed-type hypersensitivity (DTH) response was detected in pLNtx compared to mLNtx mice. Reduced IL-10 expression, reduced percentages of Tregs, and increased proportions of B cells were identified within the pLNtx. The increase of B cells resulted in a specific immunoglobulin production undetectable in mLNtx. Moreover, transferred IgG(+) cells of tolerized peripheral LN induced a strong reduction of the delayed-type hypersensitivity response, whereas CD4(+) cells were less efficient. Thus, stromal cells have a high impact on creating a unique environment. Furthermore, the environment of pLNtx induces a tolerogenic phenotype by B-cell accumulation and antibody production.
Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Manuela
M
Buettner
Reinhard
R
Pabst
Ulrike
U
Bode
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D054415:Chemokine CCL19 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D054421:Chemokine CCL21 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
D000941:Antigens; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D016207:Cytokines; C556062:IL10 protein, mouse; D007074:Immunoglobulin G; D012333:RNA, Messenger; D054400:Receptors, CCR7; D016753:Interleukin-10; D010047:Ovalbumin