Omental Milky Spots Develop in the Absence of Lymphoid Tissue-Inducer Cells and Support B and T Cell Responses to Peritoneal Antigens

Rangel-Moreno, Javier; Moyron-Quiroz, Juan; Carragher, Damian M.; Kusser, Kim; Hartson, Louise; Moquin, Amy; Randall, Troy D.

doi:10.1016/j.immuni.2009.03.014

Cited by 228 publications

(283 citation statements)

References 52 publications

(74 reference statements)

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“…Second, in the absence of an assay to reliably define LTi cell function in vitro or in vivo, it is not possible to exclude the possibility that in mice with chronic Leishmania-induced inflammation, there may be RORγ-independent development of cells that can functionally compensate for classical LTi cells. In this regard, our data are compatible with reports that tertiary lymphoid structures can develop in an LTi cell-independent manner, particularly under inflammatory conditions (66,67).…”

Section: Discussionsupporting

confidence: 92%

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Dalton¹,

Maroof²,

Owens³

et al. 2010

J. Clin. Invest.

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Receptor tyrosine kinases are involved in multiple cellular processes, and drugs that inhibit their action are used in the clinic to treat several types of cancer. However, the value of receptor tyrosine kinase inhibitors (RTKIs) for treating infectious disease has yet to be explored. Here, we have shown in mice that administration of the broad-spectrum RTKI sunitinib maleate (Sm) blocked the vascular remodeling and progressive splenomegaly associated with experimental visceral leishmaniasis. Furthermore, Sm treatment restored the integrity of the splenic microarchitecture. Although restoration of splenic architecture was accompanied by an increase in the frequency of IFN-γ + CD4 + T cells, Sm treatment alone was insufficient to cause a reduction in tissue parasite burden. However, preconditioning by short-term Sm treatment proved to be successful as an adjunct therapy, increasing the frequency of IFN-γ + and IFN-γ + TNF + CD4 + T cells, enhancing NO production by splenic macrophages, and providing dose-sparing effects when combined with a first-line immune-dependent anti-leishmanial drug. We propose, therefore, that RTKIs may prove clinically useful as agents to restore immune competence before the administration of chemo-or immunotherapeutic drugs in the treatment of visceral leishmaniasis or other diseases involving lymphoid tissue remodeling, including cancer.

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Section: Discussionsupporting

confidence: 92%

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Dalton¹,

Maroof²,

Owens³

et al. 2010

J. Clin. Invest.

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“…27 CXCL13 also contributes to the formation of B-cell follicles in nasopharynx-associated lymphoid tissue and omental milky spots. 28,29 Intestinal CPs and ILFs also depend on CXCL13 for B-cell recruitment and maturation into ILFs. CXCL13 Ϫ/Ϫ mice have normal numbers of CPs, but lack B220 ϩ ILFs, thus showing the dependence on CXCL13 for the accumulation and organization of B cells, but not the initial development of CPs.…”

Section: Discussionmentioning

confidence: 99%

Distinct Developmental Requirements for Isolated Lymphoid Follicle Formation in the Small and Large Intestine

Knoop

Butler

Kumar

et al. 2011

The American Journal of Pathology

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Cryptopatches (CPs) and isolated lymphoid follicles (ILFs) are organized intestinal lymphoid tissues that develop postnatally in mice and include stromal cells expressing the receptor activator of nuclear factor kappa-B ligand (RANKL). We investigated how stromal RANKL influences the development and differentiation of CPs and ILFs by analyzing the development of these lymphoid structures in knockout mice lacking RANKL. We found that RANKL ؊/؊ mice had a fourfold reduction in the overall density of CPs in the small intestine compared to control mice, with the largest decrease in the proximal small intestine. No B cells were present in CPs from the small intestine of RANKL ؊/؊ mice and ILF formation was completely blocked. In sharp contrast, colonic ILFs containing B cells were present in RANKL ؊/؊ mice. Stromal cells within CPs in the small intestine of RANKL ؊/؊ mice did not express CXCL13 (originally called B lymphocyte chemoattractant) and often lacked other normally expressed stromal cell antigens, whereas colonic lymphoid aggregates in RANKL ؊/؊ mice retained stromal CXCL13 expression. The CXCL13-dependent maturation of precursor CPs into ILFs is differentially regulated in the small intestine and colon, with an absolute requirement for RANKL only in the small intestine.

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“…However, they can be evaluated as lymphoid cell aggregates with secondary characteristic due to their response to local antigenic stimulus. Recently, Rangel-Moreno et al (2009) provided compelling data suggesting that omental milky spots are unique secondary lymphoid organs in mice. In this study, germinative center was not detected in the BSA injected group of rats and quails one week after injection.…”

Section: Groupmentioning

confidence: 99%

A comparative study of local defense spots within the peritoneal cavity in Japanese quails,Coturnix coturnix japonica(Galliformes, Phasianidae) and Wistar rats,Rattus norvegicus(Rodentia, Muridae)

Saydam

Eren

2012

Italian Journal of Zoology

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The local defense spots (milky spot) are found on the greater omentum but also in other peritoneal regions, as well as on the pleura and pericardium. Milky spots are small accumulations of leukocytes scattered around the capillaries. The most frequent cells in milky spots are the macrophages, followed by lymphocytes and mast cells. In this study, the structure of milky spots of quails and rats after antigenic stimulation with bovine serum albumin were examined at the light microscope levels by applying conventional histochemical and immunohistochemical methods. The parietal peritoneum and mesentery samples from quails and parietal peritoneum, mesentery and omentum majus samples from rats were collected. Local defense spots were seen as local lymphoid cell aggregations in the omentum, mesentery and parietal peritoneum in rats, whereas in quails they were seen only in the mesentery. After the bovine serum albumin injection, the dimensions of spots were at their biggest 6 hours after injection (p < 0.001) in the rat and 1 hour after injection (p < 0.01) in the quail. Lymphocytes, macrophages (MHC II positive cells in quail), plasma cells and mast cells were detected within the aggregates of both rat and quails. In conclusion, it was determined that the quails have local defense spots at the mesentery like the milky spots of rats. In addition, the present study findings confirm that local defense spots react to antigenic stimulation by innate and adaptive immunity in rats and quails.

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Omental Milky Spots Develop in the Absence of Lymphoid Tissue-Inducer Cells and Support B and T Cell Responses to Peritoneal Antigens

Cited by 228 publications

References 52 publications

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice

Distinct Developmental Requirements for Isolated Lymphoid Follicle Formation in the Small and Large Intestine

A comparative study of local defense spots within the peritoneal cavity in Japanese quails,Coturnix coturnix japonica(Galliformes, Phasianidae) and Wistar rats,Rattus norvegicus(Rodentia, Muridae)

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