Limits...
Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase.

Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH - J. Exp. Med. (2003)

Bottom Line: Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST).RIPLT alpha beta pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLT alpha pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent.These data highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis supporting the notion that HEC-6ST-dependent luminal PNAd is under regulation by LT alpha beta.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

ABSTRACT
Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LT alpha beta's activities in lymphoid organogenesis, mice simultaneously expressing LT alpha and LT beta under rat insulin promoter II (RIP) control were compared with RIPLT alpha mice in a model of lymphoid neogenesis and with LT beta-/- mice. RIPLT alpha beta pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLT alpha pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent. In contrast to the predominant abluminal PNAd pattern of HEV in LT beta-/- MLN and RIPLT alpha pancreatic infiltrates, PNAd was expressed at the luminal and abluminal aspects of HEV in wild-type LN and in RIPLT alpha beta pancreata, coincident with HEC-6ST. These data highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis supporting the notion that HEC-6ST-dependent luminal PNAd is under regulation by LT alpha beta.

Show MeSH

Related in: MedlinePlus

LTαβ contributes to luminal PNAd expression on HEV. PNAd expression was detected by immunohistochemistry analysis with MECA 79 antibody in C57BL/6 PLN (A and B), RIPLTα pancreas (C and D), RIPLTαβ pancreas (E and F), and LTβ−/− MLN (G and H). LTβ−/− MLN exhibited a reduction in luminal MECA 79 expression. RIPLTαβ pancreata exhibited an increase in the number of MECA 79+ vessels and in luminal PNAd expression compared with the predominately abluminal pattern observed in RIPLTα pancreatic infiltrates. Objective 20× (A, C, E, and G); objective 40× (B, D, F, and H).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2193975&req=5

fig5: LTαβ contributes to luminal PNAd expression on HEV. PNAd expression was detected by immunohistochemistry analysis with MECA 79 antibody in C57BL/6 PLN (A and B), RIPLTα pancreas (C and D), RIPLTαβ pancreas (E and F), and LTβ−/− MLN (G and H). LTβ−/− MLN exhibited a reduction in luminal MECA 79 expression. RIPLTαβ pancreata exhibited an increase in the number of MECA 79+ vessels and in luminal PNAd expression compared with the predominately abluminal pattern observed in RIPLTα pancreatic infiltrates. Objective 20× (A, C, E, and G); objective 40× (B, D, F, and H).

Mentions: Previous studies of the RIPLTα mouse had revealed MAdCAM-1 and abluminal PNAd expression on HEV-like vessels at the sites of transgene expression (27, 33; Fig. 5, C and D) . In the RIPLTαβ pancreas immunohistochemistry with MECA 367 antibody also revealed high levels of MAdCAM-1 within and around the infiltrates of the islet (unpublished data). Furthermore, consistent with the high number of L-selectin+ cells (Table I), there was intense luminal MECA 79 staining in RIPLTαβ pancreata with a few vessels displaying only abluminal MECA 79 (Fig. 5, E and F) as determined by immunohistochemistry. This is in contrast to the predominately abluminal MECA 79 pattern in the RIPLTα pancreas (Fig. 5, C and D; reference 33). This pericellular (i.e., luminal and abluminal) MECA 79 staining pattern in RIPLTαβ infiltrates was clearly different from that of RIPLTα pancreata and highly reminiscent of a mature LN (Fig. 5, A and B). In addition, RIPLTαβ pancreatic infiltrates exhibited an increase in the number of MECA 79+ vessels when compared with RIPLTα infiltrates. To further investigate a role for LTβ in luminal PNAd expression, immunohistochemistry with MECA 79 was performed on LTβ−/− MLNs. In contrast to the pericellular MECA 79 staining pattern on almost all wild-type LN–HEV (Fig. 5, A and B), abluminal MECA 79 staining was seen on many LTβ−/− MLN–HEV and there was a corresponding 20% reduction in L-selectin+ cells in the MLN (Fig. 5, G and H, and unpublished data).


Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase.

Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH - J. Exp. Med. (2003)

LTαβ contributes to luminal PNAd expression on HEV. PNAd expression was detected by immunohistochemistry analysis with MECA 79 antibody in C57BL/6 PLN (A and B), RIPLTα pancreas (C and D), RIPLTαβ pancreas (E and F), and LTβ−/− MLN (G and H). LTβ−/− MLN exhibited a reduction in luminal MECA 79 expression. RIPLTαβ pancreata exhibited an increase in the number of MECA 79+ vessels and in luminal PNAd expression compared with the predominately abluminal pattern observed in RIPLTα pancreatic infiltrates. Objective 20× (A, C, E, and G); objective 40× (B, D, F, and H).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193975&req=5

fig5: LTαβ contributes to luminal PNAd expression on HEV. PNAd expression was detected by immunohistochemistry analysis with MECA 79 antibody in C57BL/6 PLN (A and B), RIPLTα pancreas (C and D), RIPLTαβ pancreas (E and F), and LTβ−/− MLN (G and H). LTβ−/− MLN exhibited a reduction in luminal MECA 79 expression. RIPLTαβ pancreata exhibited an increase in the number of MECA 79+ vessels and in luminal PNAd expression compared with the predominately abluminal pattern observed in RIPLTα pancreatic infiltrates. Objective 20× (A, C, E, and G); objective 40× (B, D, F, and H).
Mentions: Previous studies of the RIPLTα mouse had revealed MAdCAM-1 and abluminal PNAd expression on HEV-like vessels at the sites of transgene expression (27, 33; Fig. 5, C and D) . In the RIPLTαβ pancreas immunohistochemistry with MECA 367 antibody also revealed high levels of MAdCAM-1 within and around the infiltrates of the islet (unpublished data). Furthermore, consistent with the high number of L-selectin+ cells (Table I), there was intense luminal MECA 79 staining in RIPLTαβ pancreata with a few vessels displaying only abluminal MECA 79 (Fig. 5, E and F) as determined by immunohistochemistry. This is in contrast to the predominately abluminal MECA 79 pattern in the RIPLTα pancreas (Fig. 5, C and D; reference 33). This pericellular (i.e., luminal and abluminal) MECA 79 staining pattern in RIPLTαβ infiltrates was clearly different from that of RIPLTα pancreata and highly reminiscent of a mature LN (Fig. 5, A and B). In addition, RIPLTαβ pancreatic infiltrates exhibited an increase in the number of MECA 79+ vessels when compared with RIPLTα infiltrates. To further investigate a role for LTβ in luminal PNAd expression, immunohistochemistry with MECA 79 was performed on LTβ−/− MLNs. In contrast to the pericellular MECA 79 staining pattern on almost all wild-type LN–HEV (Fig. 5, A and B), abluminal MECA 79 staining was seen on many LTβ−/− MLN–HEV and there was a corresponding 20% reduction in L-selectin+ cells in the MLN (Fig. 5, G and H, and unpublished data).

Bottom Line: Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST).RIPLT alpha beta pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLT alpha pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent.These data highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis supporting the notion that HEC-6ST-dependent luminal PNAd is under regulation by LT alpha beta.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

ABSTRACT
Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LT alpha beta's activities in lymphoid organogenesis, mice simultaneously expressing LT alpha and LT beta under rat insulin promoter II (RIP) control were compared with RIPLT alpha mice in a model of lymphoid neogenesis and with LT beta-/- mice. RIPLT alpha beta pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLT alpha pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent. In contrast to the predominant abluminal PNAd pattern of HEV in LT beta-/- MLN and RIPLT alpha pancreatic infiltrates, PNAd was expressed at the luminal and abluminal aspects of HEV in wild-type LN and in RIPLT alpha beta pancreata, coincident with HEC-6ST. These data highlight distinct roles of LT alpha and LT alpha beta in lymphoid organogenesis supporting the notion that HEC-6ST-dependent luminal PNAd is under regulation by LT alpha beta.

Show MeSH
Related in: MedlinePlus