[Increased revenues from secondary diagnoses : A comparison from dermatology, ophthalmology, and infectious diseases]. / Mehrerlöse durch Nebendiagnosen : Ein Vergleich von Dermatologie, Ophthalmologie und Infektiologie.

BACKGROUND: Hospital revenues generated by diagnosis-related groups (DRGs) are in part dependent on the coding of secondary diagnoses. Therefore, more and more hospitals trust specialized coders with this task, thereby relieving doctors from time-consuming administrative burdens and establishing a highly professionalized coding environment. However, it is vastly unknown if the revenues generated by the coders do indeed exceed their incurred costs. METHODS: Coding data from the departments of dermatology, ophthalmology, and infectious diseases from Rostock University Hospital from 2007-2016 were analyzed for the effects of secondary diagnoses on the resulting DRG, i. e., hospital charges. RESULTS: Ophthalmological case were highly resistant to the addition of secondary diagnoses. In contrast, adding secondary diagnoses to cases from infectious diseases resulted in 15% higher revenues. Although dermatological and infectious cases share the same sensitivity to secondary diagnoses, higher revenues could only rarely be realized in dermatology, probably owing to a younger, less multimorbid patient population. CONCLUSION: Except for ophthalmology, trusting specialized coders with clinical coding generates additional revenues through the coding of secondary diagnoses which exceed the costs for employing these coders.

[Relevant allergans by periorbital allergic contact dermatitis. Oxybuprocain, an underestimated allergen]. / Relevante Allergene beim periorbitalen allergischen Kontaktekzem. Oxybuprocain, ein verkanntes Antigen?

BACKGROUND: Periorbital allergic contact dermatitis is a rare disease and the main differential diagnoses are atopic and seborrhoeic dermatitis. The diagnosis is based on clinical appearance, patient history and patch testing. Current systematic overviews on contact allergens involved are lacking and with changes in medical preparations, new relevant antigens may emerge. PATIENTS AND METHODS: Based on the systematic data of the information network of dermatological clinics (IVDK), patch test reactions in 48,969 patients tested between 1996 and 2000 were evaluated. A total of 763 patients suffered from periorbital dermatitis which was suspected to be due to the use of topical medication. RESULTS: The most common epidermal sensitizations in the general population were observed against nickel and fragrances. In the periorbital dermatitis group, sensitization against local anaesthetics and antibiotics was more frequent than in the general population. CONCLUSIONS: In three patients, oxybuprocain was identified as the causative agent, which has not yet been recognized as a common allergen.

Interleukin 16 expression and phenotype of interleukin 16 producing cells in Crohn's disease.

BACKGROUND: The mechanisms involved in the initiation and maintenance of Crohn's disease are poorly understood. Previous studies have demonstrated an increased number of infiltrating CD4+ T cells within the inflammatory affected bowel wall in Crohn's disease. Novel therapy approaches using anti-CD4 antibodies are thought to be effective in Crohn's disease. AIMS: Interleukin 16 (IL-16) has been characterised as a chemokine with selective chemoattraction for CD4+ inflammatory T cells. In this study, cellular expression of IL-16 in Crohn's disease and ulcerative colitis was investigated. METHODS: Expression of IL-16 was analysed in tissue samples of Crohn's disease, ulcerative colitis, and normal controls by applying reverse transcription-polymerase chain reaction, non-radioactive in situ hybridisation, and immunohistochemistry. Double staining methods were used to characterise cells expressing IL-16. The amount of infiltrating CD4+ cells was determined by immunohistochemistry and correlated with the corresponding IL-16+ cell number by step sections. RESULTS: An increased number of IL-16+ cells in Crohn's disease in comparison with ulcerative colitis and control probes was demonstrated. IL-16 was expressed by CD4 and CD8 positive T cells. In addition, in active Crohn's disease there was a substantial number of IL-16 positive mast cells. The increased number of CD4+ lymphocytes correlated positively with the increased number of IL-16 positive cells in Crohn's disease. CONCLUSION: Our results demonstrate that increased expression of IL-16 in T cells and mast cells in active Crohn's disease is associated with increased numbers of CD4+ lymphocytes. Local expression of IL-16 seems to play a significant role in the initiation and persistence of the inflammatory process in Crohn's disease, presumably by IL-16 mediated recruitment of CD4+ cells, mostly lymphocytes, into the bowel wall.

Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn's disease.

Recruitment of lymphocytes is a prominent feature of the inflammatory process in Crohn's disease (CD). The present study was undertaken to investigate the expression of the novel lymphocyte-specific chemoattractant lymphotactin (Lptn) as a potential regulatory factor for the recruitment of T cells in CD. The expression of Lptn mRNA was quantified in resection specimens of patients with CD in comparison to normal controls without signs of inflammation by real-time quantitative reverse transcriptase-polymerase chain reaction and localized by nonradioactive in situ hybridization. Furthermore, the phenotype of cells expressing Lptn mRNA was characterized. In contrast to normal controls Lptn mRNA was significantly increased in tissue samples affected by CD. Cells expressing Lptn were identified as T cells, mast cells, and unexpectedly dendritic cells. Lptn mRNA was found to be up-regulated on stimulation with phorbol-12-myristate-13-acetate and concanavalin A in T cells isolated from peripheral blood, which could be prevented by dexamethasone, cyclosporine A, and FK506. A similar regulation mechanism could be identified for the Lptn receptor GPR-5 in peripheral T cells. In addition, Lptn mRNA expression could be induced in mature monocyte-derived dendritic cells. The results indicate that local expression of Lptn by activated T cells and to a lesser extent by mast cells and dendritic cells represents a key regulator for lymphocyte trafficking and maintenance of the inflammatory process observed in CD, which might be partly mediated through an autocrine/paracrine pathway of activated T cells.

Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells.

Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcepsilonRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcepsilonRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcepsilonRI on LLDC derived from atopic dermatitis patients that express high levels of FcepsilonRI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumulation of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL-16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of FcepsilonRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcepsilonRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.

Inability to culture the dominant T-cell clone from the skin of primary cutaneous T-cell lymphoma as proven by TCR gamma-chain gene sequencing.

Molecular analysis of T-cell receptor (TCR) chain rearrangement has recently become an attractive tool for demonstrating the clonal origin of cutaneous T-cell lymphoma (CTCL) and for identifying the malignant clone at the molecular level. Over the past decade a number of attempts have been made to culture malignant CTCL cells using standard procedures and these attempts have resulted in several cell lines from the peripheral blood of Sézary syndrome, mycosis fungoides and CD30+ lymphoma patients. However, so far it has not been proven by sequence analysis that the cultured T cells truly represent the malignant cells. Aiming to functionally analyze the malignant T cells at a clonal level, we generated a total of 150 T-cell clones (TCC) from lesional skin and peripheral blood of three patients with mycosis fungoides and one patient with a CD30+ lymphoma. Cells were grown either in the presence of autologous irradiated peripheral blood feeder cells using various conditions for T-cell stimulation by direct outgrowth or from skin specimens with various cytokine combinations. In order to identify the malignant TCC we used N-region-specific PCR and compared TCR gamma-chain sequences from clones of lesional skin with in vitro-generated TCC. With the methods employed, none of the 150 established cell lines was found to be identical to the malignant TCC which was readily detected in lesional skin. Our results indicate that standard cell culture methods are not suitable for growing low-grade CTCL cells from the skin but give rise only to benign infiltrating T cells.

Interleukin 16 expression in relation to disease activity in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology characterized by an infiltration of CD4+ T lymphocytes within the rheumatoid synovium. Cytokines have been shown to play a modulatory role in the pathogenesis of RA. We analyzed the expression of a T cell derived cytokine. interleukin 16 (IL-16), in relation to disease activity to characterize its biologic function in RA. METHODS: Secreted IL-16 was measured by enzyme immunoassay in sera and synovial fluids (SF) from 25 patients with RA in comparison to 20 control samples from patients with osteoarthritis (OA). IL-16 expression in peripheral blood mononuclear cells (PBMC) was characterized by flow cytometric analysis after intracellular cytokine staining for IL-16. In synovial tissue specimens, IL-16 mRNA expression was analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In parallel, expression of IL-16 was localized in synovial tissues by in situ hybridization and immunohistochemistry. Results were analyzed in relation to disease activity. RESULTS: IL-16 was detected at significantly higher levels in sera and SF of patients with RA in comparison to OA (p < 0.001). Flow cytometry of PBMC showed that a great proportion of both CD4+ and CD8+ T cells constitutively expressed the IL-16 protein. In synovial tissues, IL-16 mRNA levels were significantly elevated in comparison to OA controls (p < 0.001). In situ hybridization for IL-16 producing cells revealed a predominant accumulation of IL- 16 positive cells within the inflammatory infiltrates. A significant correlation between IL- 16 expression and local inflammatory activity could not be established (r = 0.27, p = 0.19) by microscopic analysis of the synovial cell infiltrate. In addition, no significant association was observed between serum, SF, and synovial tissue expression of IL-16 and clinical disease activity in RA. CONCLUSION: These data suggest IL-16 might play a role in the pathogenesis of chronic inflammation in RA. The lack of significant correlation between IL-16 expression, clinical disease activity, and local inflammatory activity suggests a regulatory rather than a proinflammatory function for IL-16 in the pathogenesis of chronic synovial inflammation in RA.

Response of psoriasis to interleukin-10 is associated with suppression of cutaneous type 1 inflammation, downregulation of the epidermal interleukin-8/CXCR2 pathway and normalization of keratinocyte maturation.

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy.

Rapid quantitation of proinflammatory and chemoattractant cytokine expression in small tissue samples and monocyte-derived dendritic cells: validation of a new real-time RT-PCR technology.

The analysis of cytokine profiles plays a central part in the characterization of disease-related inflammatory pathways and the identification of functional properties of immune cell subpopulations. Because tissue biopsy samples are too small to allow the detection of cytokine protein, the detection of mRNA by RT-PCR analysis is often used to investigate the cytokine milieu in inflammatory lesions. RT-PCR itself is a qualitative method, indicating the presence or absence of specific transcripts. With the use of internal or external standards it may also serve as a quantitative method. The most widely accepted method is quantitative competitive RT-PCR, based on internal shortened standards. Recently, online real-time PCR has been introduced (LightCycler), which allows quantitation in less than 30 min. Here, we have tested its use for the analysis of cytokine gene expression in different experimental in vitro and ex vivo settings. First, we compared quantitative competitive RT-PCR with real-time RT-PCR in the quantitation of transcription levels of the CD4(+) cell-specific chemoattractant Interleukin-16 during the maturation of monocyte-derived dendritic cells, and found a good correlation between both methods. Second, differences in the amounts of IL-16 mRNA in synovial tissue from patients with rheumatoid arthritis and osteoarthritis as assessed by real-time RT-PCR paralleled differences in the level of IL-16 protein in the synovial fluid. Finally, we employed real-time RT-PCR to study the cutaneous expression of several cytokines during experimental immunomodulatory therapy of psoriasis by Interleukin-10, and demonstrate that the technique is suitable for pharmacogenomic monitoring. In summary, real-time RT-PCR is a sensitive and rapid tool for quantifying mRNA expression even with small quantities of tissue. The results obtained do not differ from those generated by quantitative competitive RT-PCR.

Graft-versus-host disease-like immunophenotype and apoptotic keratinocyte death in paraneoplastic pemphigus.

Paraneoplastic pemphigus (PP) is an autoimmune disease, which is frequently associated with non-Hodgkin's lymphoma. Autoantibodies against components of the cytoplasmic plaque of epithelial desmosomes are usually present in the sera and are believed to play a major pathogenic part in acantholysis and suprabasal epidermal blistering. However, another typical histological feature of PP, interface dermatitis with keratinocyte dyskeratosis, is shared with skin diseases that involve epithelial damage mediated by T cells. Here, we present the detailed characterization of the cutaneous T-cell response in a patient with PP and demonstrate a selective epidermal accumulation of activated CD8+ T cells together with an increased local production of interferon-gamma and tumour necrosis factor-alpha, and a strong expression of HLA-DR and ICAM-1 on keratinocytes. Apoptosis was identified as a key mechanism of keratinocyte death, and appeared independent of the FAS/FAS ligand (FAS-L) pathway, as epidermal expression of FAS was not increased compared with normal skin, and FAS-L was undetectable on the protein and mRNA level. Triple therapy with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins reduced levels of pemphigus-like autoantibodies and reversed the cutaneous inflammatory reaction leading to long-standing clinical remission. Our findings support the concept of a major contribution of cytotoxic T lymphocytes to the immunopathology of paraneoplastic pemphigus.

Expression of the CD4+ cell-specific chemoattractant interleukin-16 in mycosis fungoides.

Interleukin-16 is a soluble ligand to the CD4 molecule with chemotactic properties for CD4+ cells and a competence growth factor for CD4+ T cells, upregulating HLA-DR and the interleukin-2 receptor CD25. There is also evidence for a synergistic effect of interleukin-16 and interleukin-2 on the activation of CD4+ T cells. The infiltrate in mycosis fungoides, the most common cutaneous T cell lymphoma, is typically CD4+. We tested the possibility that interleukin-16 is involved in the formation and progression of these lesions. By reverse transcription-polymerase chain reaction, interleukin-16 mRNA was detected in 18 of 18 mycosis fungoides lesions investigated. By competitive reverse transcription-polymerase chain reaction, interleukin-16 mRNA expression increased with disease stage. Secreted interleukin-16 was detected by enzyme-linked immunosorbent assay in both Th1- and Th2-like T cell clones (as characterized by their production of interferon-gamma and interleukin-4) grown from lesional dermis and epidermis. By immunohistochemistry and in situ hybridization, infiltrating lymphocytes were the main producers of interleukin-16 whereas keratinocytes and endothelial cells remained negative. Atypical cells with convoluted nuclei were also positive. In advanced mycosis fungoides stages, many blast-like cells were positive, but some larger blasts remained negative. Interleukin-16 expression correlated positively with the expression of interleukin-2 and its receptor CD25 in individual skin lesions. Interleukin-2 expression, however, was weak or absent in samples from uninvolved skin, healthy controls and lesional psoriasis. Given the biologic properties of interleukin-16 and the parallel activation of the interleukin-2/CD25 pathway, interleukin-16 might be involved in the recruitment and stimulation of CD4+ lymphocytes in mycosis fungoides lesions and therefore contribute to the perpetuation of the associated cutaneous inflammation.

RHD genotyping in weak D phenotypes by multiple polymerase chain reactions.

BACKGROUND: Weak D phenotypes involve a quantitative variation of D. The genomic basis in weak D has been disputed, however. STUDY DESIGN AND METHODS: Five sequence-specific polymerase chain reactions (SSP-PCRs) on exons 2, 5, and 7 of the RHD gene were evaluated in 248 white and 98 Japanese blood donors and compared with the results obtained by amplification of intron 4 and serology. All methods and SSP-PCR testing on the 3' non-coding region of the RHD gene were applied to the genotyping of 94 DNA samples derived from individuals expressing weak D phenotypes. RESULTS: Concordant results were obtained with all genotyping and phenotyping methods in testing 201 D-positive and 145 D-negative donors. Four of 94 weak D samples were typed as D-negative by amplification of intron 4 and SSP-PCR on exon 5. Phenotyping with monoclonal antibodies revealed a DVI category in one of these cases and DFR phenotype in three of these cases. One weak D sample, which reacted like normal D-positive cells with all applied monoclonal antibodies, was typed falsely negative by SSP-PCR on exon 5 because of a point mutation at nucleotide 667 (T-->G) that resulted in a Phe223Val amino acid substitution. In this individual, heterozygosity was found at two other amino acid positions (Glu233Gln and Val238Met) by restriction fragment length polymorphism analysis. CONCLUSION: Genetic diversity in weak D phenotypes is rare. Only 1 of 90 true weak D phenotypes (1.1%) had a genetic variation in testing on seven gene regions of the RHD gene.

The C-terminal domain of the Gs-coupled EP4 receptor confers agonist-dependent coupling control to Gi but no coupling to Gs in a receptor hybrid with the Gi-coupled EP3 receptor.

Prostaglandin E2 receptors (EPR) belong to the family of G-protein-coupled receptors with 7 transmembrane domains. They form a family of four subtypes, which are linked to different G-proteins. EP1R are coupled to Gq, EP2 and EP4R to Gs and EP3R to Gi. Different C-terminal splice variants of the bovine EP3R are coupled to different G-proteins. A mouse EP3R whose C-terminal domain had been partially truncated no longer showed agonist-induced Gi-protein activation and was constitutively active. In order to test the hypothesis that the C-terminal domain confers coupling specificity of the receptors on the respective G-proteins, a cDNA for a hybrid rEP3hEP4R, containing the N-terminal main portion of the Gi-coupled rat EP(3beta)R including the 7th transmembrane domain and the intracellular C-terminal domain of the Gs-coupled human EP4R, was generated by PCR. HEK293 cells transiently transfected with the chimeric rEP3hEP4R cDNA expressed a plasma membrane PGE2 binding site with a slightly lower Kd value for PGE2 but an identical binding profile for receptor-specific ligands as cells transfected with the native rat EP(3beta)R. In HepG2 cells stably transfected with the chimeric rEP3hEP4R cDNA PGE2 did not increase cAMP formation characteristic of Gs coupling but attenuated the forskolin-stimulated cAMP synthesis characteristic of Gi coupling. This effect was inhibited by pre-treatment of the cells with pertussis toxin. Thus, the hybrid receptor behaved both in binding and in functional coupling characteristics as the native rat EP(3beta)R. Apparently, the intracellular C-terminal domain did not confer coupling specificity but coupling control, i.e. allowed a signalling state of the receptor only with agonist binding.

[Rh-D genotyping for exon 2, 5 and 7 of German and Japanese blood donors with sequence specific polymerase chain reaction]. / Rh-D-Genotypisierung auf Exon 2, 5 und 7 von deutschen und japanischen Blutspendern mit sequenzspezifischer Polymerasekettenreaktion.

RHD genotyping from fetal cells was applied for the detection of the RHD gene in the fetus of immunized Rh-D-negative women. Additionally, RHD genotyping was applied for the characterization of Rh-D variants. Although 44 nucleotide substitutions are known to code for 35 amino acid differences between the RHCE and the RHD gene, only a few polymorphisms have been investigated yet. We investigated 7 RHD-specific nucleotides on exons 2, 5, and 7 with sequence-specific primers and 1 nucleotide with ligation-based typing. All RHD genotyping results were correlated with serological results and established genotyping methods in 116 German and 98 Japanese blood donors, because different genetic sequences coding for Rh-D polypeptides have been described in different ethnic groups. Sequence-specific amplification of D-specific sequences was concordant with the serological result in all blood donors tested. However, ligation-based typing on exon 5 gave false-negative results in 7 donors. In summary, 5 new sequence-specific PCRs have been evaluated for further characterization of Rh-D variants. Furthermore, the methods described allow nested PCR and thus may help in determination of the fetal RhD status from maternal peripheral blood during pregnancy.

Exclusive expression of the Gs-linked prostaglandin E2 receptor subtype 4 mRNA in mononuclear Jurkat and KM-3 cells and coexpression of subtype 4 and 2 mRNA in U-937 cells.

Prostaglandin E2 (PGE2) is regarded as a potent regulator of the immune system. It can regulate apoptosis in mononuclear cells and modulate the cytokine secretion pattern from T-helper cell subpopulations via an increase in cyclic AMP (cAMP). Of the 4 PGE2 receptor subtypes (EP1-EP4) that are defined pharmacologically by their affinity to subtype-specific ligands and their coupling to G proteins, EP2 and EP4 receptors couple to Gs. It is as yet unknown which of these two receptor subtypes mediates the immunomodulatory effects. By quantitative RT-PCR, the mRNA for EP4 receptors was demonstrated and quantified in the human mononuclear cell lines Jurkat, KM-3 and U-937. However, EP2 receptor mRNA was only present in U-937 cells and was 100-fold less abundant than EP4 receptor mRNA. PGE2 increased cAMP formation with an ED50 of 50-100 nM in all cell lines. cAMP formation was inhibited by the EP4R-specific antagonist AH23848. Since AH23848 inhibited PGE2-induced cAMP formation in U-937 cells to a similar extent as in Jurkat and KM-3, EP2 receptors seem to play, if any, only a secondary role for the PGE2-mediated cAMP formation in U-937 cells.

Lymphocyte traffic through lymph nodes and Peyer's patches of the rat: B- and T-cell-specific migration patterns within the tissue, and their dependence on splenic tissue.

The migration routes of lymphocyte subsets through organ compartments are of importance when trying to understand the local events taking place during immune responses. We have therefore studied the traffic of B, T, CD4(+), and CD8(+ )lymphocytes through lymph nodes and Peyer s patches. At various time points after injection into the rat, labeled lymphocytes were localized, and their phenotype characterized in cryostat sections using immunohistochemistry. Morphometry was also performed, and the recovery of 51Cr-labeled lymphocytes in these organs was determined. B and T lymphocytes entered the lymph nodes via the high endothelial venules in similar numbers. Most B lymphocytes migrated via the paracortex (T cell area) into the cortex (B cell area), and then back in substantial numbers into the paracortex. In contrast, T lymphocytes predominantly migrated into the paracortex and were rarely seen in the cortex. No obvious differences were seen between various lymph nodes and Peyer s patches and the routes of CD4(+) and CD8(+)lymphocytes. After injection of lymphocytes into animals with autotransplanted splenic tissue, the number of B lymphocytes that had migrated into the B cell area of lymph nodes and of Peyer s patches was significantly decreased, whereas CD4(+) lymphocytes migrated in larger numbers into the T cell area of both organs.

Random entry of circulating lymphocyte subsets into peripheral lymph nodes and Peyer's patches: no evidence in vivo of a tissue-specific migration of B and T lymphocytes at the level of high endothelial venules.

Lymphocytes continuously migrate through the body and thus immune competent cells are constantly delivered to most tissues. They interact with high endothelial venules (HEV) via specific homing receptors and vascular addressins, and these molecules seem to be the reason for a preferential homing of B lymphocytes into Peyer's patches and of T lymphocytes into peripheral lymph nodes. When lymphocytes derived from lymph node cell suspensions were applied in the in vitro lymphocyte/endothelium binding assay, the well-known preference of mouse lymph node B lymphocytes for Peyer's patch HEV compared to peripheral lymph node HEV was confirmed in the rat (2.8 times). When in the same in vitro assay thoracic duct lymphocytes (TDL) were used this preference was far less obvious (1.4 times). However, by injecting rat TDL intravenously and by tracing them directly in HEV, B, T, CD4+ and CD8+ lymphocytes are seen to enter Peyer's patches and peripheral lymph nodes in vivo without preference. Thus, in contrast to lymphocytes from lymph node cell suspensions, no evidence was found of a tissue-specific migration of thoracic duct B, T, CD4+ and CD8+ lymphocytes at the HEV level. This finding demonstrates the importance of considering both experimental conditions and the cell source used when investigating lymphocyte traffic.