Histology and Ultrastructure of the Cranial Lymphohaemopoietic Tissue in Chimaera monstrosa (Pisces,Holocephali)

In the present ultrastructural study we have extended previous reports on the histological organization and cell components of the lymphohaemopoietic masses occurring in the cranium, mainly in the orbit, the preorbital canal, and the suprapalatal and coiacoid areas of the holocephalan Chimaera monstrosa. Mature and developing granulocytes, monocytes, macrophages, lymphocytes and plasma cells occur in a reticular and/or fibroblastic supporting stroma inside the cartilaginous skeleton. Heterophils, which are the most abundant granulocytes in the cranial tissue, contain two distinct cytoplasmic granular populations, whereas eosinophils show one uniformly electron dense granule type. Heterophils and eosinophils may differentiate from a common precursor producing granules of each cell type in relation to the activity of rough endoplasmic reticulum and Golgi complex. The presence of macrophages, lymphocytes and developing and mature plasma cells suggests an important role of the cranial lymphohaemopoietic tissue in eliciting the immune responses. A phylogenetical relationship between this tissue and the higher vertebrate bone marrow is proposed on the basis of histological similarities between the cell microenvironments governing haemopoietic differentiation in these organs.     

Defence mechanisms in fish

The lympho-reticular tissues in the plaice were investigated for their phagocytic properties on colloidal carbon after its intraperitoneal injection. Fish were killed at intervals ranging from 10 min to 25 days after injection. Although peritoneal macrophages constituted a large population of phagocytic cells, most of the carbon apparently gained access to the circulation as free particles and phagocytosis was performed predominantly by the ellipsoids of the spleen, the network of reticulo-endothelial (RE) cells throughout the haemopoietic tissue of the kidney, and by the RE cells occupying intermuscular spaces in the atrium of the heart. The cardiac macrophages rapidly emigrated from the organ while the carbon containing macrophages in the kidney and spleen formed aggregates in the lymphoid areas, either within or outwith pre-existing aggregates of melano-macrophages.
The possible significance of phagocyte aggregations, including melano-macrophages, in association with lymphoid elements in the kidney and spleen is discussed in the context of immune mechanisms.     

一种新的源自赤NFDA1的强血管生成抑制剂福安泰-03的分离和鉴定

从赤NFDA1软骨和去皮的软组织中分离并鉴定了一种新的强血管生成抑制剂福安泰-03(Fuantai-03, FAT-03). 利用组织匀浆、盐析、离子交换层析、疏水层析和反向层析等方法进行分离和纯化. 鸡胚绒毛尿囊膜（CAM）试验检测FAT-03对血管生成的影响. SDS-PAGE分析揭示,FAT-03为单一银染条带,分子量大约为43 000.层析洗脱实验证实,这一分子量蛋白质具有强抗血管生成活性. FAT-03的纯度进一步因其独特的N末端氨基酸序列（PFGNTHNKWKLNYSAEQEFP）而肯定.每日20、40和80μg FAT-03给药组（每胚给药3 d）对血管生成的抑制率分别为 23.6%、33.1%和50.8%. 本研究首次证实,赤NFDA1产生上述强血管生成抑制剂.     

Morphocytochemical, immunohistochemical and ultrastructural characterization of the head kidney of fat snook Centropomus parallelus

This study characterized the structure and the morphocytochemical, immunohistochemical and ultrastructural aspects of the head kidney (HK) of the fat snook Centropomus parallelus. The HK is enclosed by a thin capsule of connective tissue, from which fine trabeculae originate and branch into the interior of organ. In the parenchyma, there are aggregates of lymphoid cells containing populations of lymphocytes T immunopositive for CDRO45, in a nodular arrangement, around blood vessels and melano-macrophage centres. Among the cells that constituted these aggregates and surrounded them, were macrophages and monocytes, and their precursors, with strong immunopositivity for CD68, along with cells of the granulocytic lineage in various phases of maturation positive for lysozyme and PAS. Macrophages and chromaffin and interrenal cells are also present. Ultrastructurally, the HK comprises a reticulum-endothelial stroma consisting of endothelial cells, reticulocytes of the fibroblast type and macrophage type and a parenchyma with increased cellularity, principally blood cells of the erythrocytic, granulocytic, lymphocytic, monocytic and thrombocytic series.     

An immunohistochemical study on the postnatal development of rat nasal-associated lymphoid tissue (NALT)

Summary This study concerns the development of nasal-associated lymphoid tissue in the rat, using immuno- and enzyme-histochemical staining techniques on cryostat sections. Nasal-associated lymphoid tissue is present at birth as a small accumulation of mainly T lymphocytes and non-lymphoid cells; B cells are rare. Distinct areas of T and B cells appear at 10 days after birth; by that time high endothelial venules are also observed. Intra-epithelial lymphocytes are present, most of them being T-helper cells. ED1+ macrophages are seen throughout the tissue. The proportion of ED1+cells does not change during ontogeny. ED2+cells (tissue macrophages) are present predominantly at the border between the lymphoid tissue and the surrounding connective tissue, in all age-groups. ED3+mononuclear cells are scattered throughout the nasal-associated lymphoid tissue of young animals. Later on, the ED3+ cells migrate into the border-area between lymphoid and connective tissue. Ia+ non-lymphoid cells in the nasal lymphoid tissue increase in number during ontogeny. Only a few of them show acid phosphatase activity, indicating that the proportion of classical scavenger macrophages is low. Some of them may be antigen presenting (dendritic) cells. Ia+ dendritic cells also occur between the epithelial cells. Moreover, some epithelial cells express the Ia marker.     

Reticulum cells in the ontogeny of nasal-associated lymphoid tissue (NALT) in the rat

This study concerns the ontogeny of reticulum cells (RC) in the nasal-associated lymphoid tissue (NALT) of Wistar and Brown-Norway rats. A panel of monoclonal antibodies (mAb) directed against RC in peripheral lymphoid organs (antibodies ED10ED15) was used, together with a recently developed antibody ED17, which recognizes macrophages and Langerhans cells. Early in embryogenesis, staining with common connective tissue markers, ED14 and ED15, was found. ED17-positive cells were present before cells positive to ED1, a pan-macrophage marker, or Ia glycoproteins were observed. The first differentiation of reticulum was seen at the day of birth, when ED10 recognized a distinct area in the nasal mucosa. The first T-lymphocytes were found at the same time. Two days after birth, B-cells and ED11-positive cells were present in the NALT area. Fourteen days after birth, T- and B-cell compartments were recognizable. ED10 was found predominantly in the T-cell area and ED11 was mainly confined to the B-cell compartment. We conclude that the development of the NALT is closely accompanied by the phenotypic specialization of the reticulum. This suggests that the reticulum plays an important role in the compartmentalization of NALT tissue and in the retention of lymphocyte subsets within these compartments.     

Heterogeneity of macrophage populations in human lymphoid tissue and peripheral blood

Human lymphoid tissue and peripheral blood leukocytes were stained with six monoclonal antibodies directed against monocyte/macrophage populations. The staining pattern described by each of these monoclonal reagents was compared with the distribution of morphologically distinguishable tissue macrophages. The results show that there exists considerable heterogeneity of tissue macrophages based on the expression of surface and/or cytoplasmic antigens; furthermore, the distribution of cells bearing particular antigenic determinants is associated with distinct regions in normal lymphoid tissue. Double staining methods demonstrated that these antibodies bind to different, as well as to identical, macrophage populations. OKM-1 antibody binds predominantly to sinus histiocytes and tingible body macrophages. The Leu M-1 reagent stains interdigitating reticulum cells, while the KiM-4 antibody labels follicular dendritic cells. Leu M-3 antibody identifies cells predominantly in the germinal center, and histiocytes lining the sinuses. Both CM-1 and BRL-M.1 appear to stain tissue macrophages distributed throughout the lymphoid tissue.     

混合蛋白质体系中魟鱼和海兔肝铁蛋白释放铁的动力学研究

分别制备含有魟鱼肝铁蛋白(1iver ferritin of Dasyatis akajei,DALF)和海兔肝铁蛋白(Liver ferritin of Aplysia,ALF)的混合蛋白质体系。选用电子光谱技术和不同电子供体,研究在混合蛋白质体系中,DALF和ALF释放铁的动力学过程和规律。实验结果表明,采用Na2S2O4作为还原剂时,DALF以两相行为进行释放铁的反应;而选用抗坏血酸作为还原剂时,DALF却以一级反应动力学方式进行释放铁的反应,简化释放铁的过程。在混合蛋白质体系中且以抗坏血酸和Na2S2O4为电子供体时,ALF均以一级反应动力学过程进行释放铁的反应,认为某些蛋白质参与协助ALF释放铁反应,从而简化释放铁的过程。     

Lymphoid and non-lymphoid cells in nasal-associated lymphoid tissue (NALT) in the rat

Summary Lymphocyte and macrophage subpopulations and the stroma of mucosa-associated lymphoid tissue in the nasal cavity of the rat were examined by application of immunohistochemical and enzyme histochemical methods to cryostat sections. Nasal-associated lymphoid tissue was composed of a loose reticular network with lymphocytes and macrophages, covered by epithelium. The epithelium was infiltrated with B cells, T helper (W3/13-positive) and T suppressor/cytotoxic or large granular cells (OX8-positive), ED1-positive macrophages and Ia-positive cells. The B cell areas were populated by B cells, immunopositive for surface IgM or IgG. B cells with surface IgA or IgE were rare. Germinal centres were found infrequently. T helper cells were scattered throughout the B cell area. A few ED1-positive macrophages and ED5-positive follicular dendritic cells were observed. Strong Ia staining (mostly of B cells) was found in this area. The T cell areas contained T helper and T suppressor/cytotoxic cells in about equal amounts, and numerous ED1-positive macrophages. ED1 staining was also found in the subepithelial area. Numerous ED1-, ED2- and ED3-positive macrophages were found in the border between the lymphoid mass and the surrounding connective tissue. A few non-lymphoid cells showed weak acid phosphatase or non-specific esterase activity. The morphological observations suggest that nasal-associated lymphoid tissue plays an important role in the first contact with inhaled antigens.     

Meningeal calcification of the rat pineal organ

Summary The surface of the pineal organ of the rat is covered by a leptomeningeal tissue, the continuation of the corresponding meningeal layers of the diencephalon. The pineal leptomeninx consists of stratified arachnoid and of pia mater cells which follow the vessels into the pineal nervous tissue. The pineal arachnoid contains electron-lucent and electron dense cells differing from each other in their cytoplasmic components. Corpora arenacea of various size and density occur among these arachnoid cells and can grow into the pineal organ alongside pia mater tissue. Acervuli often form groups in circumscribed meningeal calcification foci. Concrements are absent or rare in the 1- and 2-month-old animal, while they are usually present in the 4- and 6-month-old rats.The electronmicroscopic localization of Ca-ions was studied in 2- and 4-month-old rats by potassium pyroantimonate cytochemistry. In the 4-month-old animals, arachnoid cells containing a varying amount of Ca-pyroantimonate deposits were found first of all around corpora arenacea, but there were also cells free of deposits in the close vicinity of the acervuli. Deposits were preferentially localized to the cytoplasm of electron dense arachnoid cells and to the cell membrane of electron-lucent cells. Most of the precipitates occurred in locally enlarged intercellular spaces. Here, microacervuli were found in 4-month-old animals suggesting that a calcium-rich environment was responsible for the appearance of the concrements. Intermediate stages between the small acervuli and large concentric corpora arenacea may indicate an appositional growth of the acervuli in the calcification foci. Occasionally, acervuli were also located inside meningeal cells.There was no sign of the formation of acervuli in the pinealocytes or elsewhere in the pineal nervous tissue proper, in the age interval (1- to 6-month-old animals) studied. These findings confirm the view that corpora arenacea can be produced in the rat by the pineal leptomeninx. The laboratory rat seems to be usefull in studying pineal calcification of the meningeal type.Supported by the Hungarian OTKA grant Nr. 1619 to B.V.     

Endotoxin-mediated necrosis and regression of established tumours in the mouse

Summary The fractional distribution of cardia output was measured in tumour-bearing mice treated with 50 g intravenous endotoxin, and correlated with ultrastructural changes in tumour morphology.The proportion of the cardiac output going to the tumour decreased to less than 50% of its original value by 2 h and to 10%–30% by 6 h after giving endotoxin. Because endotoxin decreases absolute cardiac output, the actual perfusion of the tumour will be considerably less than these figures suggest.The decrease in perfusion correlated closely with changes in vascular morphology. Venous congestion on the tumour edge started within 1 h of giving endotoxin and by 3 h, endothelial damage and platelet aggregates were visible. At this time, all cells, tumour, connective tissue and infiltrate in the tumour centre were dead or damaged.By 24–48 h a conspicuous infiltrate of neutrophils and macrophages was present on the edge of the tumour and many of these cells were closely related to tumour cells.We suggest that the haemorrhagic necrosis may be caused by vascular obstruction leading to hypoxia and that the subsequent regression is mediated by activated macrophages and perhaps by neutrophils.     

Macrophages in haemopoietic and other tissues of the developing mouse detected by the monoclonal antibody F4/80.

Macrophages are widely distributed in lymphohaemopoietic and other tissues of the normal and diseased adult, where they play an important role in host defence and repair. Although the development of haemopoiesis has been well studied in several species, the ontogeny of the mononuclear phagocyte system remains poorly understood. We have used a highly specific mAb, F4/80, to examine the distribution of mature macrophages in the developing mouse, with special reference to their presence in the haemopoietic microenvironment. Monocytes and macrophages were first seen in embryos on day 10 in the yolk sac and liver as well as in mesenchyme. In liver, spleen and bone marrow, there was expansion of this population associated with the initiation of haemopoiesis on days 11, 15 and 17, respectively. Macrophages in these sites formed part of the haemopoietic stroma and their extensively spread plasma membrane processes could be seen making intimate contacts with clusters of differentiating haemopoietic cells. F4/80+ cells were widely dispersed in undifferentiated mesenchymal tissue in organs such as lung, kidney and gut. Numbers of F4/80-labelled cells increased concomitantly with organ growth and local mitoses were evident, as well as actively phagocytic macrophages. Our studies establish that macrophages are among the earliest haemopoietic cells to be produced during development and that they are relatively abundant in fetal tissues in the absence of overt inflammatory stimuli. Their distribution is correlated with the sequential migration of haemopoiesis and they constitute a prominent component of the stroma in fetal liver, spleen red pulp and bone marrow. Apart from a role in haemopoietic cellular interactions, their highly developed endocytic and biosynthetic activities suggest that macrophages contribute major undefined functions during growth, turnover and modelling of fetal tissues.     

Multilocular thymic cyst with follicular lymphoid hyperplasia in a male infected with HIV. A case report with fine needle aspiration cytology

BACKGROUND: Multilocular thymic cyst with follicular lymphoid hyperplasia is a rare complication in HIV-infected patients, causing pseudotumorous enlargement of the anterior mediastinum. There have been six reported cases, all with only histologic findings. This paper reports another such case and includes perhaps the first cytologic findings on this rare entity. CASE: A 35-year-old, HIV-infected male intravenous drug abuser, who complained of worsening central chest discomfort and pain on deep inspiration, was found to have a large, septated anterior mediastinal mass. Computed tomography-guided fine needle aspiration biopsy was performed. The cytologic presentation mimicked that of thymoma, with cystic degeneration and a dual population of epithelial cells and lymphocytes as well as large aggregates of "epithelial" cells intermixed with lymphocytes in a background of macrophages and cyst fluid. Histologic examination of the resected mass revealed a multilocular thymic cyst with follicular lymphoid hyperplasia. HIV-1 core protein p24 was localized immunohistochemically in the dendritic follicular cells of the germinal centers. In retrospect, the quantity of epithelium derived from the cyst lining was too scanty for thymoma, and the presence of plasma cells and lymphohistiocytic aggregates suggested follicular lymphoid hyperplasia. CONCLUSION: Multilocular thymic cyst with follicular lymphoid hyperplasia should be considered in the differential diagnosis of an anterior mediastinal mass in HIV-infected patients after lymphoma and tuberculosis.     

Fine structural and cytochemical observations of dental epithelial cells during the enameloid formation stages in red stingrays Dasyatis akajei

The fine structure and the localization of nonspecific acid phosphatase (ACPase), nonspecific alkaline phosphatase (ALPase), and calcium-dependent adenosine triphosphatase (Ca-ATPase) activities in the dental epithelial cells in tooth germs of Dasyatis akajei in the later stages of enameloid formation were investigated. Numerous invaginations of the distal cell membrane of the inner dental epithelial (IDE) cells were observed at the early stage of enameloid maturation. The invaginations contain many fine granular and filamentous substances; the lamina densa, which was thicker during the former stages, is obscure. Granules exhibiting defined ACPase activity were usually found in the IDE cells during the stages of enameloid mineralization and maturation. IDE cells are putatively involved in the removal of degenerated enameloid matrix during these stages. Marked ALPase activity was detected at the proximal and the lateral cell membranes of the IDE cells from the late stage of enameloid matrix formation to the early stage of enameloid maturation. Strong activity of Ca-ATPase was localized at the proximal and the lateral cell membranes of the IDE cells during the stages of enameloid mineralization and maturation. ALPase and Ca-ATPase activity is probably related to crystal formation in the enameloid and the removal of degenerated enameloid matrix from the enameloid.     

Dendritic cells in the rat spleen follicles

Follicles of peripheral lymphoid organs (rat) contain a type of non-lymphoid cell which is capable of arresting antigen-antibody complexes at the cell surface. These so-called dendritic cells can be visualized in immunized rats by staining antigen-antibody complexes with immunohistoperoxidase techniques. The present study concerns a classification of these cells and comparison with known non-lymphoid cell types such as macrophages, marginal metallophils and tingible body macrophages in the rat spleen follicles. Immunoenzyme histochemical and (enzyme) histochemical techniques have been combined in the same tissue sections to correlate the functional capacity of binding immune complexes with morphological characteristics or phagocytic capacity. Dendritic cells show silver affinity but do not demonstrate a characteristic pattern of hydrolytic enzymes or phagocytosis.     

Immunological importance of the second gut segment of carp.

Lymphocytes, plasma cells, granulocytes (three to four types), macrophages and monocyte-like cells were ultrastructurally distinguished in the intestinal mucosa of carp. Neutrophilic granulocytes and lymphoid cells were present in and under the epithelium throughout the gut. In contrast to macrophages which dominated in the epithelium of the second segment, basophilic and eosinophilic granulocytes (and their intermediates) were mainly found in the connective tissue of the first segment. Applying monoclonal antibodies against serum immunoglobulin (Ig) in an immunogold technique, only a minority of lymphoid cells appeared to be Ig-immunoreactive at their external membrane, suggesting the presence of many more T than B cells in the intestinal mucosa. Except for cells which resembled immature plasma cells, plasma cells did not show, or hardly showed, Ig at their surface. In contrast with the head kidney, plasma cells with an Ig-immunoreactive cytoplasm were scarce in the intestinal mucosa. As mucosa plasma cells were regularly found with the electron microscope, they possibly contain another class of Ig. Macrophages and monocyte-like cells were also found to be Ig-immunoreactive, suggesting the presence of immune complexes at their external membrane. The immunological significance of B- and T-like lymphocytes next to immune complex-binding and antigen-presenting macrophages in the second gut segment is discussed.     

Peptidergic innervation of rat lymphoid tissue and lung: Relation to mast cells and sensitivity to capsaicin and immunization

Summary The peptidergic innervation of lymphoid tissue and the lung in relation to mast cells was studied in rat. The sensitivity of neuropeptide-containing nerves to capsaicin treatment and immunization was also examined. Measurements of the content of neurokinin A and calcitonin gene-related peptide revealed that the lung contained the highest content of both neuropeptides; lymph nodes had intermediate levels, whereas the spleen had the lowest content. Immuhohistochemistry showed that the calcitonin gene-related peptide- and neurokinin A-immunoreactive nerves in lymph nodes were mainly found around blood vessels, whereas in the lung the nerves were present within the lining respiratory epithelium, bronchial smooth muscle, around blood vessels and close to lymphoid aggregates. Combined immunohistochemistry for serotonin (5-hydroxytryptamine), as a marker for mast cells, and tachykinins or calcitonin gene-related peptide revealed that a close association was often present between the nerves and 5-hydroxytryptamine-positive cells in the bronchi of the lung, while 5-hydroxytryptamine-positive cells were not observed in lymph nodes. The neurokinin A and calcitonin gene-related peptide content in lymph nodes, spleen and lung, but not the content of neuropeptide Y, was markedly decreased by capsaicin treatment, suggesting a sensory origin for the two former peptides. Aerosol immunization increased the levels of calcitonin gene-related peptide in the lung, whereas the content in mediastinal lymph nodes was not affected. These data demonstrate a peptidergic innervation mainly of blood vessels in lymphoid tissue and a close relation between sensory nerves and mast cells as well as lymphoid aggregates in the bronchi of the lung. This further suggests that the sensory innervation of lymph nodes is mainly related to regulation of vascular tone and lymph flow. Furthermore, at the site of immunization, i.e., in the airway mucosa, sensory nerve mediators may interact both with mast cells and lymphoid cells.     

Ontogeny of American paddlefish lymphoid tissues

The temporal and spatial distribution of American paddlefish Polyodon spathula immune cell populations was determined using enzyme cytochemistry and immunohistochemistry. Monocytes and macrophages were present in the renal haematopoietic tissue, spleen, meningeal myeloid tissue, cardiac myeloid tissue and lamina propria of the spiral valve at 7 days post-hatch (dph). Immature lymphocytes were present in the renal haematopoietic tissue, spleen, meningeal myeloid tissue, cardiac myeloid tissue, thymus and lamina propria of the spiral valve at 7 dph. Type A lymphocytes (T-cell like) were demonstrated in the thymus by 21 dph. Type B immunoglobulin positive lymphocytes (B-cell like) were present in the renal haematopoietic tissue, cardiac myeloid tissue and lamina propria of the spiral valve by 7 dph, the thymus at 21 dph, the spleen by 56 dph, and were not observed in the meningeal myeloid tissue of paddlefish aged 7–28 dph. Granulocytes were present in the renal haematopoietic tissue, thymus, spleen, meningeal myeloid tissue, cardiac myeloid tissue and lamina propria of the spiral valve by 7 dph. The spleens in 7–28 dph fish were predominately red pulp. Differentiation of leukocytic and erythrocytic compartments (white and red pulp, respectively) was not apparent in the spleen until 56 dph. Remarkable thymic cortical and medullary differentiation was not yet present at 28 dph, and the thymus was not sampled at 56, 84 or 112 dph. The cardiac myeloid tissue was not developed until 56 dph. Peyer's patches were present in the lamina propria by 56 dph. Paddlefish lympho-myeloid structures are therefore slow to develop, and vaccination procedures should be performed at 2–4 months post-hatch.     

Histological and enzyme histochemical investigation of the hemal nodes of the hair goat

Abstract

We investigated the structure of the hemal node in six healthy hair goats using histological and enzyme histochemical methods. After processing, tissue sections were stained with Crossman's trichrome, Gordon-Sweet's silver and Pappenheim's panoptic stains. Alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (ACP-ase) were demonstrated in frozen sections. Hemal nodes were encapsulated by connective tissue and few smooth muscle cells. Several trabeculae originated from the capsule and extended into the hemal node. A subcapsular sinus was present beneath the capsule and was continuous with the deeper sinuses. Subcapsular and deep sinuses were filled with erythrocytes. The parenchyma consisted of lymphoid follicles, diffuse interfollicular lymphocytes and irregular wide lymphoid cords. Cortical and medullary regions were not distinct. ANAE (+) and ACP-ase (+) cells were located mainly in the germinal centers of the lymphoid follicles and also were scattered equally in the interfollicular region and lymphoid cords. Monocytes, macrophages and reticular cells displayed a diffuse positive reaction, whereas localized granular positivity was observed in lymphocytes. We demonstrated that the general structure of the hair goat hemal nodes is similar to that of other ruminant species.     

An anti-human monocyte/macrophage monoclonal antibody, reacting most strongly with macrophages in lymphoid tissue

In this report, we have described monoclonal antibody (mAb) 24 which bound specifically to a 174,000 polypeptide present on 45 +/- 16% of human monocytes. Expression of the 24 molecule increased on monocytes when they were cultured. When tissues were examined using immunohistochemical techniques, macrophages (Mph) associated with skin and with lymphoid organs strongly expressed the mAb 24 molecule, whereas, Mph in nonlymphoid organs were only weakly positive. mAb 24 reacted with cells of Mph morphology plus cells of interdigitating appearance in T-cell areas, suggesting that these cells might belong to the Mph cell lineage. There was no reaction with other types of cells, such as Langerhans cells, osteoclasts, dendritic reticulum cells, and endothelial cells. The fact that the molecule recognised by mAb 24 is particularly associated with Mph in lymphoid tissue suggests that it might have a function in immune responses.