PubMed Health⌕ Search

Biomedical subjects

J C Prinz

Publications and source records attributed to J C Prinz.

At least 19 recordsLinked to original sources
PubMed2003

[Latest aspects in psoriasis pathogenesis].

During recent years the understanding of psoriasis pathogenesis has changed essentially. Psoriasis is now considered as a T cell mediated inflammation of the skin. Genetic predisposition and microbial environment cooperate in the induction of an antigen-specific T cell mediated immune response which may persist lifelong. The phenotype of the psoriatic inflammation is determined by the particular functional differentiation of the pathogenic T cells. The progress in understanding the pathogenesis of psoriasis has identified T cells and T cell-derived cytokines as targets for causal treatment approaches that in the near future will change psoriasis therapy considerably.

Autoimmune Diseases↗
PubMed2003

The role of T cells in psoriasis.

Evidence for a key role of T cells in the pathogenesis of psoriasis has come from both experimental and clinical data. Initially, generalized immunosuppressants, intended for use in transplant settings, were found to improve clinical signs and symptoms of psoriasis. Their efficacy attracted attention to the activated T cells that are a major component of the inflammatory infiltrate of psoriatic lesions. Further research determined that T cells from patients with psoriasis could transmit disease in animal models. These findings laid the groundwork for characterizing the pathogenesis of psoriasis as immune mediated with skin-directed T cells playing a central role. Once these pathogenic T cells have entered the skin, they become activated and release cytokines and chemokines to attract other immune cells to perpetuate the inflammatory cascade. As the role of the T cell in psoriasis has evolved and understanding of immunopathology has increased, a multitude of biologic targets have been revealed. Newer strategies for the treatment of psoriasis have therefore focused on modifying T cells in this disease through direct elimination of activated T cells, inhibition of T-cell activation, or inhibition of cytokine secretion or activity. The mechanisms by which these new biologic agents act on psoriasis will affect their profile of efficacy and safety. Important selection criteria for optimal antipsoriatic therapies include long-term safety and tolerability, ability to produce long-lasting remissions, and convenient dosing regimens.

Adjuvants, Immunologic↗
PubMed2002

[Anthrenus dermatitis].

A 31-year-old male presented with widespread itchy papules, especially on the legs, which had appeared 4 weeks previously. He reported that his wife and both daughters had developed similar lesions during the last week. Numerous small beetle larvae had been detected in his apartment, which were identified as museum beetle Anthrenus museorum L. Prick test with a larva extract caused a positive prick-test reaction, followed by a papular delayed type hypersensitivity reaction. History, clinical and histological examination led to the diagnosis of papular Anthrenus-dermatitis. Eradication of the beetle larvae from the patient's apartment, followed by topical glucocorticoid therapy led to a permanent remission of the dermatitis in all household members.

Adult↗
PubMed2002

Acrodermatitis chronica atrophicans affecting all four limbs in an 11-year-old girl.

Borrelia burgdorferi is a major cause of morbidity in wooded area in western Europe and the eastern seaboard of the U.S.A. Diagnosis of late stage infection and associated disorders may be difficult and often requires an array of different diagnostic procedures. Here we report an 11-year-old girl with acrodermatitis chronica atrophicans affecting all four limbs and parts of the trunk. The diagnosis was made on the basis of clinical appearance, serological and histopathological findings, and the lesional detection of B. burgdorferi-specific gene segments by polymerase chain reaction. This very unusual, severe case illustrates that despite being a late manifestation of tick-borne B.burgdorferi infection, usually occurring in adults, acrodermatitis chronica atrophicans may already appear at a young age and may be characterized by extensive skin involvement.

Acrodermatitis↗
PubMed2001

Dominant lesional T cell receptor rearrangements persist in relapsing psoriasis but are absent from nonlesional skin: evidence for a stable antigen-specific pathogenic T cell response in psoriasis vulgaris.

In a previous study we reported that clonally expanded T cell receptor beta-chain rearrangements characterized the T cell receptor usage in skin lesions of psoriasis vulgaris and indicated antigen-specific T cell selection. To assess the relevance of clonal T cell expansion for disease progression, we now determined if select clonal T cell receptor rearrangements persisted over time and were present in nonlesional skin. Sequential biopsies were taken from psoriatic skin lesions of two patients. V-D-J junctional regions of T cell receptor beta-chain variable region gene families 2, 3, 6, 13S1, and BV17 were cloned and sequenced, as these particular BV gene families are preferentially selected in psoriatic skin lesions. The lesional T cell receptor rearrangements were compared with the T cell receptor usage in nonlesional skin and in blood. Several T cell receptor beta-chain rearrangements with high transcript frequency in the first lesional biopsy were again found in sequential lesional biopsies taken as much as 3 y later from psoriasis relapses. Only T cell receptor beta-chain rearrangements with low transcript abundance showed variability in that several clones appeared for the first time or disappeared. Although nonlesional skin also exhibited a restricted T cell receptor usage with clonal T cell receptor rearrangements, the T cell receptor usage in lesional and nonlesional skin differed nearly completely. The select lesional recurrence of identical T cell receptor rearrangements reveals that inflammation in psoriasis involves the same clonally expanded T cell populations and the same antigens over prolonged periods of time. It hereby suggests that specifically recruited and locally expanded T cell clones are permanently involved in psoriatic inflammation and may play a crucial part in disease perpetuation.

Epitopes↗
PubMed2001

Psoriasis vulgaris--a sterile antibacterial skin reaction mediated by cross-reactive T cells? An immunological view of the pathophysiology of psoriasis.

The understanding of the pathogenesis of psoriasis vulgaris has advanced significantly since the therapeutic efficacy of immunosuppressive drugs has drawn attention to the role of immune mechanisms in psoriasis manifestation. Today, the results of many experimental studies provide evidence that psoriasis is largely a T-cell mediated disorder. It may result from antigen-specific activation of T cells in the skin of genetically predisposed individuals. These T cells apparently have a particular functional differentiation and promote the psoriatic skin changes by secreting a certain set of cytokines. Based on the fact that streptococcal throat infections are a trigger of guttate psoriasis, the putative psoriatic antigens are assumed to be in keratinocyte proteins that share structural homologies with streptococcal proteins and thus induce cross-reactive responses of antibacterial T cells against skin components. Together with the particular phenotype of psoriatic skin lesions these findings suggest that psoriasis represents a sterile antibacterial tissue reaction, which is mediated by streptococci-specific T cells that cross-react against epidermal autoantigens.

Antigens, Bacterial↗
PubMed2000

Analysis of the TCRBV repertoire of T cells in normal, human skin: evidence for a restricted diversity.

Alpha beta T cells constitute an important component in the first line of immunologic defense in human skin. In order to determine the local selection forces driving T cell diversity, we studied the T cell receptor repertoire in normal human skin and compared it with that of matched blood samples. Using semiquantitative reverse transcription-polymerase chain reaction the expression of T cell receptor beta-chain V genes was determined. The majority of skin, but not blood T cells, revealed a bias towards usage of T cell receptor beta-chain V2 and V6. Whereas sequencing of T cell receptor beta-chain V2 and V6 polymerase chain reaction products showed a heterogeneous clonal distribution within these beta-chain V gene families, the analysis of other selected either over- or underrepresented beta-chain V gene families (BV3, BV12, BV13S1, BV17) revealed numerous identical T cell receptor beta-chain V transcript sequences that were not detected in blood. Restricted T cell receptor diversity in terms of beta-chain V gene preferences or clonal expansion was observed in skin samples of donors from all ages (0.5-87 y). Hence, the repertoire of T cells in normal human skin is apparently subjected to skin-specific selection throughout life. According to our data, this process could involve superantigens, which favor polyclonal accumulation of T cells using certain beta-chain V genes, as well as antigens, which induce clonal T cell expansion. Our results furthermore indicate, that T cell receptor beta-chain V repertoire restrictions do not necessarily result from disease-associated activation of the skin immune system, but could reflect regular mechanisms of immunologic homeostasis within the epithelial surface of the body.

Adolescent↗
PubMed1999

Selection of conserved TCR VDJ rearrangements in chronic psoriatic plaques indicates a common antigen in psoriasis vulgaris.

Psoriasis vulgaris is a common HLA-associated inflammatory skin disease. Although its etiology is still unknown, it is thought to involve T cell-mediated inflammatory mechanisms. In examining the lesional psoriatic TCR beta chain (TCRB) usage in a pair of identical twins concordant for psoriasis, we observed repetitive TCR VDJ rearrangements which indicated antigen-specific oligoclonal T cell expansion. Several of these TCRB rearrangements were identical or highly homologous in the amino acid composition of the complementarity determining region 3 (CDR3), suggesting that T cells with these TCR might be important for disease manifestation. This conclusion was strengthened by TCR analysis of other psoriasis patients. Several repetitive lesional TCRB rearrangements were found that were similar to the conserved CDR3 seen in the twins. Since TCR antigen specificity is largely determined by the beta chain CDR3, selection of T cells with conserved TCRB CDR3 motifs could indicate the presence of a common antigen as a major target of the lesional psoriatic immune response.

Amino Acid Sequence↗
PubMed1999

Which T cells cause psoriasis?

Today, T cells appear to be the main protagonists in the pathogenesis of psoriasis vulgaris. This article summarizes how T cells might contribute to the generation of psoriatic skin lesions. It discusses the preferential T cell receptor usage and the putative mode of T cell activation in psoriatic skin lesions, and how streptococcal throat infections could be involved in disease manifestations. The results are integrated into a pathogenetic concept which considers psoriasis as a T-cell mediated autoimmune disorder.

Autoimmune Diseases↗
PubMed1996

Treatment of severe cutaneous lupus erythematosus with a chimeric CD4 monoclonal antibody, cM-T412.

BACKGROUND: Monoclonal CD4 antibodies are among the most potent immunomodulatory agents in various experimental models of autoimmune disease, including murine lupus erythematosus. OBJECTIVE: The aim of this study was to evaluate the toxicity and therapeutic efficacy of a chimeric monoclonal CD4 antibody, cM-T412, in patients with cutaneous lupus erythematosus (LE). METHODS: Five patients with severe cutaneous LE lesions received intravenously a total of 275, 400, or 475 mg of cM-T412 in single doses of 20 to 50 mg during a period of 5 to 8 weeks. RESULTS: CD4 antibody treatment induced a long-lasting decrease in disease activity. It resulted in healing of LE skin lesions, a reconstituted responsiveness to conventional treatment, or both. Despite a substantial depletion of circulating CD4+ T lymphocytes, no clinical signs of immunosuppression were noted. CONCLUSION: Monoclonal CD4 antibodies should be considered as a novel treatment for the management of severe cutaneous LE.

Adjuvants, Immunologic↗
PubMed1995

Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris.

Psoriasis vulgaris is an inflammatory skin disease characterized by excessively increased keratinocyte proliferation. Several lines of evidence support the idea that T cells infiltrating psoriatic skin lesions play a vital role in the pathogenesis of the disease. To establish whether lesional accumulation and activation of T lymphocytes reflect a specific local immune response, the TCR beta-chain variable (V beta) region gene usage was studied in chronic psoriatic plaques, normal skin, and paired blood lymphocytes. By semiquantitative PCR, we found that overexpression of either or both V beta 2 and V beta 6 gene families characterized the TCR repertoires of normal skin and psoriatic skin lesions. However, sequence analysis of the complementarity-determining region 3 (CDR3) of these V beta gene families demonstrated a marked TCR oligoclonality only in psoriatic lesions, not in normal skin or in blood lymphocytes. The amino acid sequences of the lesional TCR clones revealed that certain conserved junctional motifs were shared by different patients. A second biopsy taken from one of the psoriasis patients 18 mo later from a different anatomical site disclosed that the same TCR clones were again dominating. These data suggest that lesional psoriatic T lymphocytes expressing the prevailing TCR V beta genes represent an oligoclonal T cell subset that expanded from a few progenitor T cells in response to Ag in the skin of psoriasis patients. They are derived from a polyclonal T cell population that, by the expression of V beta 2 or V beta 6 TCR, appears to be predisposed for homing to the skin.

Adolescent↗
PubMed1995

A reduction in allergen-induced Fc epsilon R2/CD23 expression on peripheral B cells correlates with successful hyposensitization in grass pollinosis.

BACKGROUND: The cellular basis for the mechanism of specific hyposensitization is still unclear. OBJECTIVE: We prospectively studied the effect of immunotherapy on allergen-induced proliferation and Fc epsilon R2/CD23 expression of lymphocytes. METHODS: Mononuclear cells prepared from the peripheral blood of 22 patients with grass pollen (GP) allergy before, during, and after a preseasonal immunotherapy period with GP were stimulated with GP or control antigens. Tritiated thymidine uptake and percentage of CD23+ B cells were determined daily during days 6 to 8 and compared with lymphocyte responsiveness of 11 only symptomatically treated atopic patients and 14 nonatopic individuals. RESULTS: GP-induced lymphocyte proliferative response of both hyposensitized and symptomatically treated GP-allergic patients decreased markedly before the pollen season and rose again after seasonal allergen exposure, whereas a long-lived decrease in GP-induced Fc epsilon R2/CD23+ B cells was only observed in GP-treated patients. Alterations in Fc epsilon R2/CD23 expression were closely related to changes in symptoms and medication requirement during the following pollen season. In contrast, immunotherapy had no effect on Fc epsilon R2/CD23 expression of B cells without stimulation or on B cells cultured in the presence of control antigens. CONCLUSION: Because Fc epsilon R2/CD23 expression on B cells is antagonistically regulated by the cytokines interleukin-4 and interferon-gamma, the decrease of allergen-induced Fc epsilon R2/CD23+ B cells indicates an altered cytokine secretion pattern of the allergen-specific T lymphocytes with a predominance of interferon-gamma.

Adolescent↗
PubMed1994

T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products.

Psoriasis vulgaris has been recognized lately as an immunologically mediated inflammatory skin disease. To analyze the pathogenetic role of T lymphocytes in the generation of psoriatic skin lesions, 105 T cell clones (TCC) and 10 T cell lines (TCL) were differentially isolated from dermis and epidermis of psoriatic skin specimens. Supernatants prepared from these T cells were studied for their effects on keratinocyte proliferation in vitro. Conditioned media from 14 of 77 epidermal TCC, 7 of which were CD8+, and from 8 of 28 dermal TCC, 5 of which were CD8+, reproducibly enhanced keratinocyte proliferation, with more pronounced mitogenic activities found in dermal TCC. Another 9 epidermal and 3 dermal TCC did not affect keratinocyte growth and supernatants from the remaining clones, as well as from the 5 epidermal and 5 dermal TCL, inhibited keratinocyte replication to varying degrees. Both mitogenic and suppressive activities were largely abolished by addition of an antiserum to interferon-gamma (IFN-gamma), while addition of epidermal growth factor or irradiated psoriatic TCL had little effect on the activities of the supernatants. These studies reveal that a subpopulation of lesional psoriatic T lymphocytes is capable of enhancing keratinocyte proliferation in vitro via secreted products. Their mitogenic capacity most likely requires IFN-gamma, but the ultimate effect is apparently determined by the presence of additional cytokines. Activation of T cells secreting such combinations of factors in vivo may contribute to the keratinocyte alterations characteristic of psoriatic skin lesions.

Cell Division↗
PubMed1994

T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and T helper type 2 cells.

In various immunological disorders the pathomechanisms of tissue damage are causally associated with specific patterns of locally produced cytokines. To study the molecular and cellular mechanisms involved in the manifestation of psoriasis vulgaris we have assessed the cytokine mRNA profile expressed in lesional psoriatic skin and in T cell clones (TCC) that were established from skin lesions of patients with psoriasis. As demonstrated by use of the polymerase chain reaction (PCR), psoriasis lesions consistently exhibit transcription of a complex pattern of cytokines. It includes mediators selectively produced by T lymphocytes [interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, interleukin (IL)-2, IL-3 and IL-5] as well as cytokines secreted by various cell types [transforming growth factor (TGF)-alpha/-beta, TNF-alpha, IL-6/-8 and granulocyte-macrophage-colony stimulating factor], while IL-4 is missing. With the exception of TGF-alpha, this cytokine profile was also observed in lesional psoriatic T cell clones yielding supernatants mitogenic for keratinocytes in vitro (MTCC), but not in T cell clones yielding supernatants that inhibited keratinocyte proliferation (STCC). The congruent cytokine expression of psoriatic skin lesions and MTCC emphasizes that inflammation in psoriasis is driven by a sofar unrecognized regulatory T cell subset that may serve to control epidermal regeneration and convey immunosurveillance over epithelial surfaces. It is characterized by the combined expression of IFN-gamma, TGF-beta, IL-2 and IL-5 in the absence of IL-4 and by its selective capacity to enhance keratinocyte proliferation. This newly defined combination of regulatory properties of a distinct T cell population cannot be reconciled with an immune response of the T helper cells (TH)0, TH1 or TH2 type.

Base Sequence↗
PubMed1990

Expression of the Fc-receptor for IgE (Fc epsilon RII, CD23) on alveolar macrophages in extrinsic allergic alveolitis.

Expression of the Fc receptor for IgE (Fc epsilon R) was analyzed on alveolar macrophages (AM) in 10 patients with extrinsic allergic alveolitis (EAA) compared with 10 patients with sarcoidosis and to 6 apparently healthy controls. By using the anti-Fc epsilon RII mAb M-L25 in immunocytochemistry experiments, we found that greater than 60% of AM in 10 of 10 patients with EAA were strongly positive, as evidenced by visual analysis in light microscopy and by cytometry. By contrast, no significant staining was detected in sarcoidosis or in controls with either method. Similar results were obtained when Fc epsilon R were identified with preformed immune complexes consisting of NIP-specific human/mouse chimeric IgE antibody plus NIP-ovalbumin. Furthermore, greater than 60% of AM in patients with EAA stained positive for IgE, demonstrating that endogenous IgE is bound to the AM. Our data suggest that IgE antibodies bound to Fc epsilon RII on AM may be involved in pathophysiology of extrinsic allergic alveolitis by activation of the AM after binding of allergen to the cell surface IgE. Furthermore, with the clearcut pattern of Fc epsilon RII expression in extrinsic allergic alveolitis it may be possible to use CD23 antibodies for differential diagnosis of inflammatory lung disease.

Adult↗
PubMed1990

Allergen-directed expression of Fc receptors for IgE (CD23) on human T lymphocytes is modulated by interleukin 4 and interferon-gamma.

T lymphocytes bearing Fc receptors (FcR) for immunoglobulins are known to have immunoglobulin class-specific regulatory functions. Here we report that expression on T cells of the low-affinity FcR for IgE (Fc epsilon RII/CD23) is preferentially induced by stimulation with antigens that cause an IgE response. T cells from eight patients allergic to the hemoglobin of Chironomus thummi thummi mosquito larvae (CHIT I) were analyzed for reactivity with the anti-FcERII/CD23 monoclonal antibody (mAb) M-L25 under various conditions. No Fc epsilon RII/CD23+ T cells were observed among freshly isolated, resting peripheral blood mononuclear cells (PBMC). Stimulation of PBMC with CHIT I, however, induced a marked although transient Fc epsilon RII/CD23 expression on a large portion of the allergen-activated T lymphocytes. It reached a maximum of 37.2 +/- 4.6% Fc epsilon RII/CD23+ T cell blasts on day 5 of culture. The selectivity of this expression became evident when compared to non-allergenic control antigens: after stimulation of PBMC with tetanus toxoid or purified protein derivative from tuberculin a maximum of 4.6% +/- 1.4% and 4.2% +/- 1.1% T cell blasts was found to express Fc epsilon RII/CD23, respectively. Activation by an anti-CD3 mAb was insufficient to induce Fc epsilon RII/CD23 on T cells. The allergen-stimulated Fc epsilon RII/CD23+ T cells exclusively belonged to the CD4+CD29+ helper inducer T cell subset. Using a cDNA probe coding for the B cell Fc epsilon RII/CD23, Northern blot analysis revealed a 1.7-kb Fc epsilon RII/CD23 mRNA in extracts of highly purified allergen-stimulated T cells. It was of the same size as Fc epsilon RII/CD23 mRNA of the lymphoblastoid B cell line WI-L2. Of several cytokines tested [interleukin (IL) 1 to IL 6, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha] only IL 4 and IFN-gamma significantly modified allergen-induced Fc epsilon RII/CD23 expression on T cells. The latter was enhanced nearly twofold in the presence of IL 4, and was almost completely abrogated by IFN-gamma. IL 4, however, could not increase the number of Fc epsilon RII/CD23+ T lymphocytes either alone or in combination with an anti-CD3 mAb. Taken together, the selective induction of Fc epsilon RII/CD23 on T cells by allergen and its inclusion in the regulatory network of cytokines point to an important role of Fc epsilon RII/CD23+ T lymphocytes in the human IgE response.

Allergens↗