Involvement of brown adipose tissue in subcutaneous fat necrosis of the newborn.

BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is a rare condition that manifests within days after birth. The interscapular region, axillae and shoulders are the most commonly affected sites, corresponding to anatomic sites of brown adipose tissue (BAT) in newborns. OBJECTIVE: We postulated a specific involvement of BAT in SCFN and searched for brown adipocytes at affected sites. METHODS: Biopsy specimens were immunostained with antibodies against uncoupling protein 1 (UCP-1) and examined by electron microscopy. We also examined BAT by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and computed tomography (PET-CT) scanning. RESULTS: A few cells in biopsy specimens from two patients bound antibodies against UCP-1, and brown adipocytes were detected at several stages of degeneration. PET-CT scans revealed lower uptake of (18)F-FDG at major sites of SCFN. CONCLUSION: SCFN and BAT can be found at the same sites, suggesting a pathophysiological connection.

Influence of T cell receptor V alpha expression on Mlsa superantigen-specific T cell responses.

Recognition of conventional foreign antigen by T cells is determined by the expression of multiple variable regions of both alpha and beta chains of the T cell receptor (TCR) alpha/beta heterodimer. In contrast, there exists a class of antigens that appears to interact with the TCR alpha/beta heterodimer through the variable region on the beta chain (V beta), independent of other TCR components, a property that has led to their designation as superantigens. The goal of the present study was to analyze V alpha use in V beta 6+ T cells responsive to the superantigen, Mlaa. Results indicate that while deletion of T cells expressing V beta 6 in Mlsa-expressing mice is essentially complete and therefore appears to occur regardless of V alpha usage, in vitro Mlsa stimulation of T cells from Mlsa-negative mice results in significant skewing of V alpha use among responding V beta 6+ T cells. This indicates that V alpha expression influences recognition of the superantigen, Mlsa by mature peripheral T cells.

Expression of H-Y antigen by female mice carrying Sxr.

The minor transplantation antigen H-Y can cause graft rejection and can stimulate the generation of H-2-restricted T cell responses. We have used both responses to type karyotypically abnormal mice for the presence of H-Y antigen, in order to investigate the role of H-Y in sex determination. The mice under scrutiny were Sxr5-carrying females derived by crossing females carrying the T(16;X)16H translocation with Sxr carrying males. These females were fully fertile and were H-Y positive. These results are consistent with the testis determining gene, Tdy, which may or may not be H-Y, having a threshold effect on testis differentiation during embryogenesis. They also show that the presence of H-Y in adult females does not impair reproduction.

Minor transplantation antigens: their role in shaping the T cell repertoire.

Minor transplantation, or histocompatibility (H), antigens are the targets of host-versus-graft (hvg) and graft-versus-host (gvh) reactions that occur when organs or tissues are exchanged between members of the same species who, although genetically not identical, are matched for their major histocompatibility complex (MHC) encoded transplantation antigens. Genes encoding minor H antigens map outside the MHC, on a number of different chromosomes. Whilst gvh and hvg reactions against individual minor H antigens are relatively weak, certainly in comparison with such reactions against MHC antigens, the presence of multiple minor H differences (the situation encountered in man) gives rise to very vigorous reactions that can endanger the survival of graft or host, or both. This is the pathological role of minor H antigens and, indeed, it was this role which was first designated to the MHC antigens, before their physiological role as guidance molecules for T lymphocytes was discovered. Recently, a potential physiological role for minor H antigens has been uncovered by the finding that the presence of certain minor H alleles in mice leads to removal in the thymus (negative selection) of all those T cells expressing a particular T cell receptor (TCR) gene. Such cells therefore never reach the periphery, where they might otherwise give rise to autoimmune reactions. The T cell repertoire is thus moulded by at least some minor H antigens, which may therefore be regarded as non-MHC immune response genes. Furthermore, T cell receptor usage by T cells specific for allogeneic minor H antigens appears not to be representative of T cell receptor usage in the peripheral pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous ligands selecting T cells expressing particular V beta elements.

It has recently become clear that the minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands which lead to the partial or total deletion of T cells bearing particular V beta segments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple V beta 11 and V beta 3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the V beta 11/V beta 3 deleting ligands identify them as members of the superantigen family. Bacterial superantigens are known to bind both MHC class II and the TCR in regions distinct from conventional peptide antigens. Within the MMTV genome, the 3' LTR has been identified as encoding superantigen function. We present data demonstrating that in vitro translation identifies the major product of the open reading frame (ORF) within the 3' LTR as a type II integral membrane glycoprotein. It is proposed that the type II membrane glycoprotein interacts with MHC and TCR in a manner analogous to the bacterial superantigens and distinct from conventional peptide antigen. Several unanswered questions regarding superantigen action remain; what determines total or partial deletion? How is Mls transferred between cells? These questions are addressed in the discussion.

An immature rat lymphocyte marker CD157: striking differences in the expression between mice and rats.

We have established a novel monoclonal antibody that recognises mouse and rat CD157, and uncovered striking differences in both the level and stage of expression of this antigen in the primary lymphoid organs between these two species. Unlike mouse, the majority of rat thymocytes express CD 157. SHR and WKY rats were the exception, having unusually low levels (similar to those of the mouse) of these cells. However, in both species, a subset of CD3- CD4- CD8- thymocytes exhibited high levels of CD157. Surprisingly, these CD157high cells temporarily upregulated MHC class I molecules in both species. Furthermore, a third of CD157high rat thymocytes were CD45RC+, a marker found on immature thymocytes with regenerative capacity. Examination of the bone marrow lymphoid population shows that the expression of rat CD157 is largely observed at the CD45R+ IgM- pre-B-II cell stage, and unlike mouse, extension of expression into the IgM+ immature B cell stage was marginal. Similar to CD157high immature thymocytes, these immature B cells also expressed high levels of MHC class I. With the exception of the LEC, SHR and WKY rat strains, which have three- to four-fold less CD157+ bone marrow myeloid cells, percentages of these cells are similar between these two species. Thus, marked differences in the level and stage(s) of CD157 expression on lymphoid cells in mouse and rat indicate that CD157 may not, as previously thought, have a direct role in T or B cell differentiation.

Adenoid cystic carcinoma of the external auditory canal: correlation between histological features and MRI appearances.

A rare case of adenoid cystic carcinoma of the external auditory canal with magnetic resonance imaging appearances is reported. Both T1 weighted and T2 weighted MR images showed the tumour as a hypointense mass, although there was marked contrast enhancement. Microscopic examination of the resected tumour showed a preponderance of solid tumour cell nests. According to previous reports, these pathological and radiological findings indicate a poor prognosis.

I-J revisited: is the I-J genetic restriction in downregulation due to an endogenous superantigen analogous to mammary tumour virus (Mtv)-encoded endogenous superantigen?

This article puts forward the hypothesis that the I-J genetic restriction observed between certain downregulatory (suppressor) T cells and antigen presenting cells is due to an endogenous superantigen analogous to the mouse mammary tumour virus (Mtv) products encoded by the open reading frames in the 3' long terminal repeat (LTR) of mtv's. In its weak form this hypothesis asserts that the I-J genetic restriction is due to an endogenous superantigen ligand on antigen presenting cells, which crosslinks the V beta and/or V alpha chains of certain T cell receptors (TCR) with major histocompatibility complex (MHC) class II, and that MHC together with this superantigen ligand causes positive selection of T cells bearing the appropriate I-J+ TCR in the thymus. In the periphery these T cells recognize peptide/MHC complex in the presence of the superantigen. In its strong form the hypothesis states that this superantigen ligand for TCR and MHC is encoded by integrated virus genome, e.g. Mtv. These possibilities can now be approached experimentally and their exploration may uncover one of the ways in which T cells are assigned to different functions, including downregulation.

Percutaneous retrieval of intracardiopulmonary artery metallic needle (Kirschner's wire): a case report.

We report a case of successful percutaneous retrieval of a broken Kirschner's wire that had entered the venous system and the right atrium and later migrated to the left pulmonary artery. The management of a long, rigid, nail-like foreign body within the heart and/or the pulmonary artery is discussed.

Appendiceal abscess mimicking infected urachal cyst in a child with intestinal malrotation.

An appendiceal abscess with intestinal malrotation can occur anywhere in the abdomen, not only in the right lower quadrant. We report a case presenting a midline mass of the lower abdomen whose computed tomography (CT) and ultrasonography (US) findings mimicked a urachal abscess. A retrospective review of CT findings led to the correct diagnosis by showing malposition of the ascending colon.

Leiomyoma of the parapharyngeal space.

A rare case of leiomyoma of the prestyloid parapharyngeal space is reported together with computed tomographic and magnetic resonance imaging findings. The tumor appeared as a well-circumscribed ovoid mass with some calcifications and lobulations. Because the attenuation, signal intensity, and shape of the mass were not specific and were similar to those of a pleomorhic adenoma, the most common tumor of the prestyloid parapharyngeal space, radiological differentiation of leiomyoma from pleomorphic adenoma of the prestyloid parapharyngeal space was difficult.

[Recent progress in superantigen research].

In 1993 there was substantial progress in superantigen research. The following are the main achievements. (i) The life cycle of an exogenous mouse mammary tumor virus, MMTV (SW), has been clearly eluciated. (ii) X-ray crystallography of toxic shock syndrome toxin 1 has been completed. (iii) The involvement of a superantigen encoded by an endogenous mouse mammary tumor virus, Mtv-51, in the development of a B cell lymphoma has been shown in SJL mice. However, there are many unsolved questions. For example, (i) are there endogenous superantigens in man? (ii) is there any role for superantigens in the development of autoimmunity? (iii) what is the three dimensional structure of superantigens encoded by mouse mammary tumor viruses? In the near future superantigens will be exploited for therapeutic purposes in the area of autoimmunity and cancer.

T-cell receptor expressed on an autoreactive T-cell clone, clone 4. I. Induction of various T-receptor functions by anti-T idiotypic antibodies.

Three monoclonal antibodies (1G3, 2H11, and 3G12) specific for a syngeneic Ek-specific T-cell clone, clone 4, have been established. The antibodies specifically blocked not only the activation of the clone in response to the specific antigen Ek but also the activation by IL-2. Kinetic studies of the blocking activity revealed that the antibodies blocked activation not only through steric hindrance of the antigen-binding site of the receptor but also via inhibition of DNA synthesis. The antibodies induced unresponsiveness of the clone to the specific antigen Ek, but not to nonspecific activation by IL-2. The state of unresponsiveness induced by 1G3 continued for 14 days, the longest time so far examined. The recovery from the unresponsiveness (tolerance) was not observed unless the clone cells proliferated vigorously in response to IL-2. The idiotope recognised by 1G3 was different from that by 2H11 and/or 3G12. This might explain some functional differences elicited by the antibodies.

Positive selection of V beta 2+ CD8+ T cells.

T cells bearing V beta 4, V beta 6, V beta 10, V beta 14, and V beta 17a are positively selected by MHC class I and/or class II molecules with poorly elucidated mechanisms. In this paper levels of V beta 2+ CD4+ and V beta 2+ CD8+ T cells from 33 inbred, five F1 hybrid, and 48 [(C58 x DBA/2)F1 x DBA/2] backcross mice have been examined. The results show that (i) V beta 2+ CD8+ T cells are positively selected by MHC class I H-2k molecules, (ii) this positive selection might be mediated by a non-H-2 ligand(s) in association with the Kk molecule, and (iii) inbred strains of mice, so far examined, do not have endogenous superantigens for deletion of V beta 2+ T cells.

Down-regulation of the T cell receptor by a mitogenic anti-Thy-1 antibody.

Antigen-specific unresponsiveness lasting at least 2 weeks can be induced in a T cell clone by 24-h pretreatment with mitogenic anti-T cell receptor antibodies. In this report the relationship is explored between the antigen-specific unresponsiveness and activation pathways triggered via the T cell receptor and Thy-1: the latter pathway is dependent on the former. A mitogenic anti-Thy-1 antibody (KT16) made the T cell clone unresponsive to specific antigen and to an anti-T cell receptor antibody coupled to Sepharose. The unresponsiveness lasted for at least 7 days. However, cells made unresponsive to specific antigen in these ways (the T cell receptor and Thy-1) could be activated by both interleukin 2 and KT16. KT16 down-modulated the T cell receptor immediately after the pretreatment, but not on day 7 after the pretreatment. These facts indicate that the state of the unresponsiveness was caused by blocking transduction of an activation signal triggered by the T cell receptor to an activation pathway shared by the T cell receptor and Thy-1.

Negative selection of Tcra-V8+CD8+ T cells by MHC class I molecules.

Tcrb-V-specific positive and negative selection of T cells has been well documented. In contrast, nothing is known about Tcra-V-specific selection. Using Tcra-V8-specific KT50 antibody Tcra-V8-specific selection of T cells has been examined. The CD8+ T cell subpopulation bearing Tcra-V8 are shown to be negatively selected by major histocompatibility complex (MHC) class I H-2Kd and H-2Dd/Ld molecules. Furthermore, percentages of these T cells are also influenced by Tcra-V haplotypes. Involvement of non-H-2 self (super)antigens in this MHC class I restricted negative selection, however, remains to be determined.

Antigen and MHC restriction specificity of two types of cloned male-specific T cell lines.

Two types of H-Y antigen-specific cloned T cell lines were established. Clone 2-1 is an IAb restricted proliferating T cell line and clone 10-2 is an H-2Db restricted proliferating and cytotoxic T cell line. Clone 2-1 proliferated in response to H-Y antigen with an IAb restriction in the absence of IL 2. IAb mutant B6.C-H-2bm12 (bm12) mice did not stimulate this clone. This defect may be the cause of the unresponsiveness to H-Y antigen with cytotoxic T lymphocytes (CTL) in bm 12 mice (i.e., the failure of activation of H-Y-specific helper T cells). Although (B10.A X bm12)F1 mice are known to show functional complementation, as demonstrated by the presentation of insulin to helper T cells and the H-Y-specific CTL response, the F1 male cells could not stimulate this clone. The IA determinant restricting H-Y antigen presentation to helper T cells and/or the H-Y antigenic determinant seems to differ between C57BL/6 (B6) and the F1 mice. Monoclonal anti-IAb antibodies but not anti-H-Y antibodies blocked the proliferation of this clone. The clone had no cytotoxic activity unless Con A was added to the cytotoxicity assay culture. Clone 10-2 proliferated in response to H-Y antigen with an H-2Db restriction. Proliferation was not observed unless specific stimulator cells and IL 2 were supplied to the culture; IL 2 alone could not support this clone. The clone did not respond to male cells from the H-2Db mutant B6.C-H-2bm14 (bm14). The clone had cytotoxic activity against male H-2Db+ cells but not against male bm14 cells. This evidence indicates that the mutation of bm14 occurred in the structural gene coding for a molecule on which a determinant restricting the recognition of H-Y antigen by B6 CTL exists. The phenotypes of clone 2-1 were Thy-1.2+, Ly-1.2-, Ly-2.2-, IAb-, and H-2Kb+, and the phenotypes of clone 10-2 were Thy-1.2+, Ly-1.2-, Ly-2.2+, IAb-, and H-2Kb+.

Cytotoxic T cells generated in the autologous mixed lymphocyte reaction. I. Primary autologous mixed lymphocyte reaction.

In the course of the culture of an autologous mixed lymphocyte reaction (AMLR), T cells proliferated in response to autologous non-T cells, and differentiated to cytotoxic T cells (AMLR killers). DNA synthesis was necessary to generate AMLR killers, as the elimination of autoreactive proliferating cells with BUdR and UV light completely abrogated AMLR killer cytolysis. Amlr killers lysed various lymphoid cell lines, including autologous B cell lines, autologous or allogeneic mitogen blasts stimulated by Con A, PHA, or pokeweed mitogen, variious nonlymphoid cell lines derived from human, mouse, or rat, and weakly normal autologous or allogeneic non-T cells. KMT-17, methylcholanthrene-induced rat fibrosarcoma, was the only resistant cell line to have been tested. AMLR killers had characteristics similar to NK cells, Major histocompatibility antigens were not the target antigens for AMLR killers. AMLR killers distinguished the blasts stimulated by alloantigens as self from the blasts stimulated by mitogens as non-self.

Epitope-specific binding of CD8 regulates activation of T cells and induction of cytotoxicity.

Functions of the CD8 molecule were examined to determine whether CD8 is merely a ligand-binding molecule and/or is involved in signal transduction. Using KT112 (anti-CD8 beta), CD8 was demonstrated to transduce an activation signal leading to cytotoxicity. Conformational changes of the CD8 molecule might be responsible for the activation, because (i) KT15 (anti-monomorphic CD8 alpha), but not antibodies specific for polymorphic CD8 alpha determinants, abrogated KT112 (anti-CD8 beta)-induced cytotoxicity without blocking the binding of KT112, whilst (ii) KT112 (anti-CD8 beta) inhibited KT15 (anti-monomorphic CD8 alpha)-mediated augmentation of proliferation triggered by a V beta 11-specific antibody without blocking the binding of KT15.