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Biomedical subjects

C M Parker

Publications and source records attributed to C M Parker.

At least 19 recordsLinked to original sources
PubMed2001

Intestinal mast cell progenitors require CD49dbeta7 (alpha4beta7 integrin) for tissue-specific homing.

Mast cells (MCs) are centrally important in allergic inflammation of the airways, as well as in the intestinal immune response to helminth infection. A single lineage of bone marrow (BM)-derived progenitors emigrates from the circulation and matures into phenotypically distinct MCs in different tissues. Because the mechanisms of MC progenitor (MCp) homing to peripheral tissues have not been evaluated, we used limiting dilution analysis to measure the concentration of MCp in various tissues of mice deficient for candidate homing molecules. MCp were almost completely absent in the small intestine but were present in the lung, spleen, BM, and large intestine of beta7 integrin-deficient mice (on the C57BL/6 background), indicating that a beta7 integrin is critical for homing of these cells to the small intestine. MCp concentrations were not altered in the tissues of mice deficient in the alphaE integrin (CD103), the beta2 integrin (CD18), or the recombination activating gene (RAG)-2 gene either alone or in combination with the interleukin (IL)-receptor common gamma chain. Therefore, it is the alpha4beta7 integrin and not the alphaEbeta7 integrin that is critical, and lymphocytes and natural killer cells play no role in directing MCp migration under basal conditions. When MCp in BALB/c mice were eliminated with sublethal doses of gamma-radiation and then reconstituted with syngeneic BM, the administration of anti-alpha4beta7 integrin, anti-alpha4 integrin, anti-beta7 integrin, or anti-MAdCAM-1 monoclonal antibodies (mAbs) blocked the recovery of MCp in the small intestine. The blocking mAbs could be administered as late as 4 d after BM reconstitution with optimal inhibition, implying that the MCp must arise first in the BM, circulate in the vasculature, and then translocate into the intestine. Inasmuch as MCp are preserved in the lungs of beta7 integrin-deficient and anti-alpha4beta7 integrin-treated mice but not in the small intestine, alpha4beta7 integrin is critical for tissue specific extravasation for localization of MCp in the small intestine, but not the lungs.

Animals↗
PubMed2001

Integrin alpha E(CD103)beta 7 mediates adhesion to intestinal microvascular endothelial cell lines via an E-cadherin-independent interaction.

Integrins are important for T cell interactions with endothelial cells. Because the integrin alpha(E)beta(7) is expressed on some circulating gut-homing T cells and as T cell numbers are reduced in the intestinal lamina propria of alpha(E)-deficient mice, we evaluated whether alpha(E)beta(7) mediates binding to intestinal endothelial cells. We found that anti-alpha(E)beta(7) mAbs partially blocked the binding of cultured intraepithelial T cells to human intestinal microvascular endothelial cells (HIMEC). Furthermore, alpha(E)beta(7)-transfected K562 cells bound more efficiently than vector-transfected K562 cells to HIMEC. Finally, HIMEC bound directly to an alpha(E)beta(7)-Fc fusion protein. These interactions were partially blocked by anti-alpha(E)beta(7) mAbs, and endothelial cell binding to the alpha(E)beta(7)-Fc was dependent upon the metal ion-dependent adhesion site within the alpha(E) A domain. Of note, the HIMEC lacked expression of E-cadherin, the only known alpha(E)beta(7) counterreceptor as assessed by functional studies, flow cytometry, and RT-PCR. Thus, HIMEC/alpha(E)beta(7) binding was independent of E-cadherin. In addition, this interaction appeared to be tissue selective, as HIMEC bound to the alpha(E)beta(7)-Fc, whereas microvascular endothelial cells from the skin did not. Finally, there was evidence for an alpha(E)beta(7) ligand on intestinal endothelial cells in vivo, as alpha(E)beta(7) expression enhanced lymphocyte binding around vessels in the lamina propria in tissue sections. Thus, we have defined a novel interaction for alpha(E)beta(7) at a nonepithelial location. These studies suggest a role for alpha(E)beta(7) in interactions with the intestinal endothelium that may have implications for intestinal T cell homing or functional responses.

Antibodies, Blocking↗
PubMed2001

Role of integrin alphaE(CD103)beta7 for tissue-specific epidermal localization of CD8+ T lymphocytes.

Tissue-specific T cell localization is crucial for immune surveillance of normal tissues and the pathogenesis of inflammatory disorders. In psoriatic skin, CD8+ lymphocytes predominantly reside within the epidermis, whereas CD4+ T cells are most abundant within the dermis. Molecular mechanisms guiding this spatial compartmentalization are not completely understood, however. Here, we demonstrate that 55% (+/-9.7%, n = 14) of the epidermal T cells, predominantly of the CD8+ phenotype, expressed the integrin alphaE(CD103)beta7. In contrast, only 5% (+/-2.0%) of the dermal T cells were alphaE(CD103)beta7+. Integrin alphaE(CD103)beta7 was not detected in normal skin (n = 10), and less than 1% of peripheral blood lymphocytes derived from normal (n = 11) or psoriatic (n = 10) donors expressed alphaE(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor beta1, expression of integrin alphaE(CD103)beta7 was induced on 52.8% (+/-16.2%) of CD8+ cells, but only on 6.1% (+/-2.3%) of CD4+ cells, suggesting selective inducibility on CD8+ lymphocytes. Whereas similar overall expression of transforming-growth-factor-beta1-specific mRNA was detected in normal and psoriatic skin by real-time quantitative polymerase chain reaction, immunohistochemistry revealed focal overexpression of transforming growth factor beta1 underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor beta1 expression may contribute to induction of alphaE(CD103) in vivo. Adhesion of transforming-growth-factor-beta1-stimulated CD8+, but not CD4+, T cells to cultured keratinocytes and psoriatic epidermis in frozen sections could be significantly inhibited by antibodies that blocked the alphaE(CD103)/E-cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of alphaE(CD103)beta7 expression in some cases. Overall, integrin alphaE(CD103)beta7 appears to contribute to tissue-specific epidermal localization of CD8+ T lymphocytes.

Antigens, CD↗
PubMed2000

Cutaneous inflammatory disorder in integrin alphaE (CD103)-deficient mice.

The integrin alpha(E)beta(7) is thought to play an important role in the localization of mucosal, but not of cutaneous T lymphocytes. Thus, it was surprising that 89% of adult alpha(E)(-/-) mice on the 129/Sv x BALB/c background developed inflammatory skin lesions without an apparent infectious etiology. Skin inflammation correlated with alpha(E) deficiency in mice with a mixed 129/Sv x BALB/c background, but not in mice further backcrossed to BALB/c and housed in a second animal facility. These studies suggested that alpha(E) deficiency, in combination with other genetic and/or environmental factors, is involved in lesion development. The lesions were infiltrated by CD4(+) T cells and neutrophils, and associated with increased expression of inflammatory cytokines. Furthermore, skin inflammation resulted from transfer of unfractionated alpha(E)(-/-) splenocytes into scid/scid mice, but not from transfer of wild-type splenocytes, suggesting that the lesions resulted from immune dysregulation. We also studied the role of alpha(E)beta(7) in a murine model of hyperproliferative inflammatory skin disorders that is induced by transfer of minor histocompatibility-mismatched CD4(+)/CD45RB(high) T cells into scid/scid mice under specific environmental conditions. Under housing conditions that were permissive for lesion development, transfer of alpha(E)-deficient CD4(+)/CD45RB(high) T cells significantly exacerbated the cutaneous lesions as compared with lesions observed in mice reconstituted with wild-type donor cells. These experiments suggested that alpha(E)-expressing cells play an important role during the course of cutaneous inflammation. In addition, they suggest that alpha(E)beta(7) deficiency, in combination with other genetic or environmental factors, is a risk factor for inflammatory skin disease.

Adoptive Transfer↗
PubMed2000

In vivo roles of integrins during leukocyte development and traffic: insights from the analysis of mice chimeric for alpha 5, alpha v, and alpha 4 integrins.

Mice chimeric for integrins alpha(5), alpha(V), or alpha(4) were used to dissect the in vivo roles of these adhesion receptors during leukocyte development and traffic. No major defects were observed in the development of lymphocytes, monocytes, or granulocytes or in the traffic of lymphocytes to different lymphoid organs in the absence of alpha(5) or alpha(V) integrins. However, in agreement with previous reports, the absence of alpha(4) integrins produced major defects in development of lymphoid and myeloid lineages and a specific defect in homing of lymphocytes to Peyer's patches. In contrast, the alpha(4) integrin subunit is not essential for localization of T lymphocytes into intraepithelial and lamina propria compartments in the gut, whereas one of the partners of alpha(4), the beta(7) chain, has been shown to be essential. However, alpha(4)-deficient T lymphocytes cannot migrate properly during the inflammatory response induced by thioglycolate injection into the peritoneum. Finally, in vitro proliferation and activation of lymphocytes deficient for alpha(5), alpha(V), or alpha(4) integrins upon stimulation with different stimuli were similar to those seen in controls. These results show that integrins play distinct roles during in vivo leukocyte development and traffic.

Animals↗
PubMed2000

Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity.

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

Animals↗
PubMed2000

Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation.

HIV particles that use the chemokine receptor CXCR4 as a coreceptor for entry into cells (X4-HIV) inefficiently transmit infection across mucosal surfaces [1], despite their presence in seminal fluid and mucosal secretions from infected individuals [2] [3] [4]. In addition, although intestinal lymphocytes are susceptible to infection with either X4-HIV particles or particles that use the chemokine receptor CCR5 for viral entry (R5-HIV) during ex vivo culture [5], only systemic inoculation of R5-chimeric simian-HIV (S-HIV) results in a rapid loss of CD4(+) intestinal lymphocytes in macaques [6]. The mechanisms underlying the inefficient capacity of X4-HIV to transmit infection across mucosal surfaces and to infect intestinal lymphocytes in vivo have remained elusive. The CCR5 ligands RANTES, MIP-1alpha and MIP-1beta suppress infection by R5-HIV-1 particles via induction of CCR5 internalization, and individuals whose peripheral blood lymphocytes produce high levels of these chemokines are relatively resistant to infection [7] [8] [9]. Here, we show that the CXCR4 ligand stromal derived factor-1 (SDF-1) is constitutively expressed by mucosal epithelial cells at sites of HIV transmission and propagation. Furthermore, CXCR4 is selectively downmodulated on intestinal lymphocytes within the setting of prominent SDF-1 expression. We postulate that mucosally derived SDF-1 continuously downmodulates CXCR4 on resident HIV target cells, thereby reducing the transmission and propagation of X4-HIV at mucosal sites. Moreover, such a mechanism could contribute to the delayed emergence of X4 isolates, which predominantly occurs during the later stages of the HIV infection.

Chemokine CXCL12↗
PubMed2000

Human intestinal lamina propria and intraepithelial lymphocytes express receptors specific for chemokines induced by inflammation.

To determine which chemokine receptors might be involved in T lymphocyte localization to the intestinal mucosa, we examined receptor expression on human intestinal lamina propria lymphocytes (LPL), intraepithelial lymphocytes (IEL) and CD45RO+beta7hi gut homing peripheral blood lymphocytes (PBL). Virtually all LPL and IEL expressed CXCR3 and CCR5, receptors that have been associated with Th1(Tc1)/Th0 lymphocytes, while CCR3 and CCR4, receptors associated with Th2 (Tc2)lymphocytes, CCR7, CXCR1 and CXCR2 were not expressed. CXCR3 and CCR5 receptors were functional, as LPL and IEL migrated to their respective ligands I-TAC and RANTES. In addition, most alphaEbeta7- LPL and IEL expressed high levels of CCR2. While the majority of CD45RO(-)beta7hi PBL also expressed CXCR3 and CCR5, a proportion of these cells were CXCR3- and/or CCR5- and some expressed CCR4 and/or CCR7, indicating that lymphocytes recruited to the intestinal mucosa represent a subset of these cells. In summary, our results show that LPL and IEL within the normal intestine express a specific and similar array of chemokine receptors whose ligands are constitutively expressed in the intestinal mucosa and whose expression is up-regulated during intestinal inflammation. These results support the view that CXCR3, CCR5 and CCR2 may play an important role in lymphocyte localization within the intestinal mucosa.

Animals↗
PubMed2000

T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines.

The epithelia are the avascular layers of cells that cover the environment-exposed surfaces of the body. It appears that T cells localize to selected sites in or adjacent to epithelia via the selective expression of adhesion molecules and chemokine receptors on T cells. These bind to counter-receptors and to chemokines expressed by epithelial cells. Recently, there has been an advance in our understanding of the interaction of the alpha(Ebeta7) integrin with its epithelial cell ligand, E-cadherin. In addition, a new adhesion molecule has been identified on non-intestinal epithelial cells, termed lymphocyte-endothelial-epithelial-cell adhesion molecule (LEEP-CAM). Finally, there have been advances in our understanding of the role of skin- or gut-epithelia-derived chemokines in regulating activated T cell homing to these sites.

Animals↗
PubMed1999

Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis.

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen-positive (CLA(+)) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic alpha4beta7(-)CLA(-) memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti-GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.

Antibodies, Monoclonal↗
PubMed1999

Lymphocyte adhesion to epithelia and endothelia mediated by the lymphocyte endothelial-epithelial cell adhesion molecule glycoprotein.

Upon encountering the relevant vascular bed, lymphocytes attach to endothelial adhesion molecules, transmigrate out of circulation, and localize within tissues. Lymphocytes may then be retained at microanatomic sites, as in tissues, or they may continue to migrate to the lymphatics and recirculate in the blood. Lymphocytes also interact transiently, but with high avidity, with target cells or APC that are infected with microbes or have taken up exogenous foreign Ags. This array of adhesive capabilities is mediated by the selective expression of lymphocyte adhesion molecules. Here, we developed the 6F10 mAb, which recognizes a cell surface glycoprotein designated lymphocyte endothelial-epithelial cell adhesion molecule (LEEP-CAM), that is distinct in biochemical characteristics and distribution of expression from other molecules known to play a role in lymphocyte adhesion. LEEP-CAM is expressed on particular epithelia, including the suprabasal region of the epidermis, the basal layer of bronchial and breast epithelia, and throughout the tonsillar and vaginal epithelia. Yet, it is absent from intestinal and renal epithelia. Interestingly, it is expressed also on vascular endothelium, especially high endothelial venules (HEV) in lymphoid organs, such as tonsil and appendix. The anti-LEEP-CAM mAb specifically blocked T and B lymphocyte adhesion to monolayers of epithelial cells and to vascular endothelial cells in static cell-to-cell binding assays by approximately 40-60% when compared with control mAbs. These data suggest a role for this newly identified molecule in lymphocyte binding to endothelium, as well as adhesive interactions within selected epithelia.

Antibodies, Blocking↗
PubMed1999

Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice.

The mucosal lymphocyte integrin alpha E(CD103)beta 7 is thought to be important for intraepithelial lymphocyte (IEL) localization or function. We cloned the murine integrin gene encoding alpha E, localized it to chromosome 11, and generated integrin alpha E-deficient mice. In alpha E-/- mice, intestinal and vaginal IEL numbers were reduced, consistent with the known binding of alpha E beta 7 to E-cadherin expressed on epithelial cells. However, it was surprising that lamina propria T lymphocyte numbers were diminished, as E-cadherin is not expressed in the lamina propria. In contrast, peribronchial, intrapulmonary, Peyer's patch, and splenic T lymphocyte numbers were not reduced in alpha E-deficient mice. Thus, alpha E beta 7 was important for generating or maintaining the gut and vaginal T lymphocytes located diffusely within the epithelium or lamina propria but not for generating the gut-associated organized lymphoid tissues. Finally, the impact of alpha E deficiency upon intestinal IEL numbers was greater at 3-4 wk of life than in younger animals, and affected the TCR alpha beta+ CD8+ T cells more than the gamma delta T cells or the TCR alpha beta+ CD4+CD8- population. These findings suggest that alpha E beta 7 is involved in the expansion/recruitment of TCR alpha beta+ CD8+ IEL following microbial colonization. Integrin alpha E-deficient mice will provide an important tool for studying the role of alpha E beta 7 and of alpha E beta 7-expressing mucosal T lymphocytes in vivo.

Animals↗
PubMed1999

The role of beta7 integrins in CD8 T cell trafficking during an antiviral immune response.

The requirement of beta7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I-restricted T cell receptor for antigen were rendered deficient in expression of all beta7 integrins or only the alphaEbeta7 integrin. To quantitate the relative use of beta7 integrins in migration in vivo, equal numbers of OT-I and OT-I-beta7(-/-) or OT-I-alphaE-/- lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-beta7(-/-) LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, beta7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, beta7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was beta7 integrin-mediated. The alphaEbeta7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of alphaEbeta7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also alphaEbeta7 independent.

Animals↗
PubMed1998

Direct and regulated interaction of integrin alphaEbeta7 with E-cadherin.

The cadherins are a family of homophilic adhesion molecules that play a vital role in the formation of cellular junctions and in tissue morphogenesis. Members of the integrin family are also involved in cell to cell adhesion, but bind heterophilically to immunoglobulin superfamily molecules such as intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, or mucosal addressin cell adhesion molecule (MadCAM)-1. Recently, an interaction between epithelial (E-) cadherin and the mucosal lymphocyte integrin, alphaEbeta7, has been proposed. Here, we demonstrate that a human E-cadherin-Fc fusion protein binds directly to soluble recombinant alphaEbeta7, and to alphaEbeta7 solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY' cells expressing the alphaEbeta7 integrin adhere strongly to purified E-cadherin-Fc coated on plastic, and the adhesion can be inhibited by antibodies to alphaEbeta7 or E-cadherin. The binding of alphaEbeta7 integrin to cadherins is selective since cell adhesion to P-cadherin-Fc through alphaEbeta7 requires >100-fold more fusion protein than to E-cadherin-Fc. Although the structure of the alphaE-chain is unique among integrins, the avidity of alphaEbeta7 for E-cadherin can be regulated by divalent cations or phorbol myristate acetate. Cross-linking of the T cell receptor complex on intraepithelial lymphocytes increases the avidity of alphaEbeta7 for E-cadherin, and may provide a mechanism for the adherence and activation of lymphocytes within the epithelium in the presence of specific foreign antigen. Thus, despite its dissimilarity to known integrin ligands, the specific molecular interaction demonstrated here indicates that E-cadherin is a direct counter receptor for the alphaEbeta7 integrin.

Amino Acid Sequence↗
PubMed1997

Powered functional endoscopic sinus surgery.

The use of powered instrumentation in functional endoscopic sinus surgery has been a revolutionary development in the surgical treatment of chronic sinusitis. Several studies have demonstrated the safety, efficacy, and ease of use of this new technique. To provide support and coordinate the surgical process in powered functional endoscopic sinus surgery procedures, perioperative nurses must have an appreciation for its specific equipment handling and for appropriate patient care. This article describes a specific protocol that perioperative nurses can use to facilitate efficient and safe surgical environments for patients who undergo powered endoscopic sinus surgery procedures.

Chronic Disease↗
PubMed1997

Internal validity of the disruptive behavior disorder symptoms: implications from parent ratings for a dimensional approach to symptom validity.

A dimensional approach was used to evaluate the internal validity of the DSM-III-R ADHD-inattention, ADHD-hyperactivity/impulsivity, oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms (i.e., whether a symptom has a stronger correlation with its own dimension that the other three). Parents rated 4,019 children between the ages of 2 and 19 on these symptoms. The results showed that 5 of the 6 inattention symptoms, 3 of the 4 hyperactivity symptoms, 1 of the 4 impulsivity symptoms, 6 of the 9 oppositional defiant disorder symptoms, and 8 of the 11 CD symptoms had significant internal validity. Confirmatory factor analysis (CFA) found support for inattention, hyperactivity/impulsivity, oppositional defiant, and conduct disorder dimensions. Multiple-group CFA also found support for factor pattern and loading invariance across gender. The implications of these results as well as the merits of the dimensional approach to symptom validity are discussed in the context of the DSM-IV changes in ADHD, ODD, and CD.

Adolescent↗
PubMed1997

Murine psoriasis-like disorder induced by naive CD4+ T cells.

Psoriasis is a complex disorder involving alterations of many cell types. Although evidence suggests a T-cell pathogenesis for psoriasis, a primary role of T cells has not been directly demonstrated. Here, we show that reconstitution of scid/scid mice with minor histocompatibility mismatched naive CD4+ T lymphocytes resulted in skin alterations that strikingly resembled human psoriasis clinically, histopathologically and in cytokine expression. This skin disorder was diminished when memory T cells were coinjected. Thus, a subset of dysregulated CD4+ T cells can cause tissue alterations seen in psoriasis without the presence of CD8+ cells or a primary epithelial abnormality.

Animals↗