Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The circulating lymphoid cells of eight consecutive untreated infants with severe combined immunodeficiency disease (SCID) with B cells were analyzed for surface marker expression and function. The B cells of these children expressed sIg, HLA-DR, CD19 (B4), CD20 (B1), CD21 (B2), Leu-8, and lacked expression of CD10 (CALLA), as do normal peripheral blood B lymphocytes. SCID B cells also expressed antigens that are normally absent or present on only a minor subset of circulating adult B lymphocytes, including CD1c (M241), CD38 (OKT10), CD23 (PL13), with or without concomitant CD5 (Leu-1) expression. The B cells of these children were capable of proliferating in vitro when stimulated with Staphylococcus aureus Cowan I. However, in the presence of pokeweed mitogen, S. aureus Cowan I, and normal T cells, the sIg+ cells of these children produced only IgM. Studies performed on normal B cells obtained from cord blood, young children, and adults reveal that whereas cord blood B cells are predominantly CD1c, CD38, and CD23 positive, B-cell expression of these antigens decreases with age. Cord blood B cells, similar to SCID B cells, produce only IgM when stimulated in vitro with pokeweed mitogen and S. aureus Cowan I. Based on these observations, we hypothesize that SCID B cells represent a population of B cells present during normal B-cell ontogeny which becomes a minor subset when an individual develops full immunologic competence.
 ...
PMID:Characterization of B cells in severe combined immunodeficiency disease. 267 Aug 51

Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.
 ...
PMID:Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients. 912 Mar 8

In vivo infection with human immunodeficiency virus type 1 (HIV-1) leads to gradual depletion of CD4+ T lymphocytes from the peripheral blood and later from the lymphoid organs. The mechanism of CD4 cell depletion is not known. HIV can only replicate in dividing lymphocytes, but greater than 98% of the lymphocytes in vivo at any given time are resting and are not permissive for productive infection. We found that exposure of resting CD4+ T lymphocytes to HIV-1 transiently upregulated expression of cell surface CD62L (L-selectin), the receptor for homing to lymph nodes, with concomitant enhanced ability of these cells to bind to lymph node high endothelial venules in an ex vivo homing assay (increased approximately 12-fold, P < 0.001) and to home from the blood into lymph nodes following intravenous injection into SCID mice. This suggested the possibility that decreases in numbers of CD4+ T lymphocytes in the blood of HIV-1-infected subjects may reflect enhanced homing of abortively infected, resting lymphocytes into lymph nodes rather than direct virus replication in and killing of these cells, and may explain development of lymphadenopathy at a time when numbers of CD4+ T lymphocytes in the blood fall.
 ...
PMID:HIV induces homing of resting T lymphocytes to lymph nodes. 912 20

Defects of the common gamma chain subunit of the cytokine receptors (gamma c) or of Jak3, a tyrosine kinase required for gamma c signal transduction, result in T-B+ severe combined immunodeficiency (SCID). However, atypical cases, characterized by progressive development of T lymphocytes, have been also reported. We describe a child with SCID caused by Jak3 gene defects, which strongly but not completely affect Jak3 protein expression and function, who developed a substantial number (> 3,000/microL) of autologous CD3+CD4+ T cells. These cells showed a primed/activated phenotype (CD45R0+ Fas+ HLA-DR+ CD62L(lo)), defective secretion of T-helper 1 and T-helper 2 cytokines, reduced proliferation to mitogens, and a high in vitro susceptibility to spontaneous (caused by downregulation of bcl-2 expression) as well as activation-induced cell death. A restricted T-cell receptor repertoire was observed, with oligoclonal expansion within each of the dominant segments. These features resemble those observed in gamma c-/y and in Jak3-/- mice, in which a population of activated, anergic T cells (predominantly CD4+) also develops with age. These results suggest that residual Jak3 expression and function or other Jak3-independent signals may also permit the generation of CD4+ T cells that undergo in vivo clonal expansion in humans; however, these mechanisms do not allow development of CD8+ T cells, nor do they fully restore the functional properties of CD4+ T lymphocytes.
 ...
PMID:Development of autologous, oligoclonal, poorly functioning T lymphocytes in a patient with autosomal recessive severe combined immunodeficiency caused by defects of the Jak3 tyrosine kinase. 944 56

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+ cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV- cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 alpha and beta chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).
 ...
PMID:Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. 947 33

Recently, we reported that abortive HIV infection of resting human T lymphocytes up-regulated expression of CD62L, the receptor for homing to lymph nodes (LNs), and enhanced homing of these cells from the blood into the LNs (Wang et al., 1997, Virology 228:141). This suggested that HIV-induced homing of resting lymphocytes (which comprise >98% of all lymphocytes) may be a major mechanism for the reduction of CD4+ lymphocytes in the blood of infected individuals. This mechanism also could be partially responsible for the lymphadenopathy that often develops at the same time that CD4+ lymphocytes are disappearing from the blood. In this study, we show that secondary signaling through the homing receptors (CD62L, CD44, CD11a) of abortively infected resting CD4+ T lymphocytes induced apoptosis. These signals would occur as the cells home into the LNs. Apoptosis did not occur after secondary signaling through some other receptors (CD26, CD4, CD45, and HLA class I) or in HIV-exposed resting CD8+ lymphocytes signaled through the homing receptors. These findings indicate that HIV-induced homing of resting CD4+ lymphocytes to LNs results in death of many of these cells. This was confirmed in the LNs of SCID mice that were i.v. injected with HIV-exposed resting human lymphocytes. Thus, these effects of HIV upon binding to resting CD4+ T lymphocytes, which are not permissive for HIV replication, may significantly contribute to their depletion in vivo. These findings also offer an explanation for the bystander effect observed in the LNs of AIDS patients, whereby cells not making virus are dying.
 ...
PMID:A novel mechanism of CD4 lymphocyte depletion involves effects of HIV on resting lymphocytes: induction of lymph node homing and apoptosis upon secondary signaling through homing receptors. 988 95

The nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenotransplantation model is increasingly utilized to study both human lymphohematopoietic stem/progenitor cells and committed cell types. Human B lymphoid cells develop and proliferate in this model. We found high numbers of CD19+CD5+ B lymphoid cells in the bone marrows and spleens of NOD/SCID mice transplanted with human CD34+ stem/progenitor cells. The CD5+ cells accounted for a particularly large percentage of the B lymphoid cells in the spleens of chimeras analyzed three months after transplantation. CD19+CD5+ cells from all the analyzed chimeras coexpressed HLA-DR, surface IgM, CD20, CD38, CD43, and CD45. However, CD19+CD5+ cells were negative for kappa light chain, CD10, CD11a, CD11b, CD15, CD21, CD22, CD23, CD25, CD34, CD35, CD44, CD62L, CD69, and CD71. Cell surface expression of the lambda light chain, surface IgD, CD9, and CD40 antigens was detected in some but not all chimeras. Thus, the CD19+CD5+ cell population detected in our study has the phenotype of previously described CD5+ B lymphoid cells in humans and other species. The origin and role of the B lymphoid cells which express CD5 cell surface glycoprotein are poorly understood. The malignant cells in B lymphoid chronic lymphocytic leukemia express CD5, and the numbers of CD5+ B lymphoid cells are elevated in several autoimmune conditions. The human-NOD/SCID chimera system may provide an in vivo model to investigate the maturation and development of this cryptic human CD5+ B lymphoid cell subpopulation.
 ...
PMID:Human hematopoietic stem/progenitor cells generate CD5+ B lymphoid cells in NOD/SCID mice. 1052 59

The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)-4 and transforming growth factor (TGF)-beta activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L(+) CD4(+) T cells exacerbated colitis in reconstituted SCID mice, T-bet-deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet-deficient CD62L(-) CD4(+) T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta responses and the development of chronic intestinal inflammation in T cell-mediated colitis. Furthermore, TGF-beta was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-beta and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell-mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.
 ...
PMID:The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. 1199 18

A mutation (c.878T>A) in the common gamma chain (gamma(c)) causes an X-linked combined immunodeficiency (XCID) in a large kindred of British origin. In the disease, gamma(c) is expressed, but its binding to Jak3 is reduced. The immune deficiencies and clinical course were less marked in toddlers and school age children with XCID(L293Q) than in severe combined immunodeficiency (SCID). However, affected newborns were profoundly deficient in thymic size and T cells. In some affected infants, thymic size and numbers of T cells gradually increased during the first year. Their clinical course was relatively benign. In affected infants of one lineage, the number of blood T cells failed to increase substantially. They succumbed to opportunistic infections. T cell deficiencies in XCID(L293Q) progressively worsened during adolescence. Decreased thymic function, failure to rescue T cells from apoptosis, and replication senescence were possible causes. Blood T cells with the phenotype CD45RA(+)CD62L(+) (unstimulated T cells) were most depressed. CD4(+) T cells were also deficient in a specific marker of recent thymic emigrants, episomal DNA deletion circles created during TcR gene rearrangements. Apoptosis of T cells was increased, but neither apoptosis nor cell death was age-related. In contrast, telomere shortening in T cells increased with age. Unlike murine gamma(c) gene deletions, gamma delta T cells were prominent in affected adolescents and young adults. Furthermore, T cells with a V delta 2/V gamma 9 specificity declined with age and were replaced in the oldest male with a V delta 1 specificity. Thus, the mutation provides many insights concerning the role of gamma(c) in the biology of T cells.
 ...
PMID:Immune consequences of mutations in the human common gamma-chain gene. 1212 29

Primary effusion lymphoma (PEL) is recognized as a unique lymphoma entity, which occurs exclusively in body cavities as a serous lymphomatous effusion without tumor formation or organ infiltration. We established a cell line of B-cell origin from a pericardial effusion of a 63-year-old Japanese PEL patient who did not have human immunodeficiency virus infection. This PEL cell line had human herpesvirus-8 (HHV-8) and Epstein-Barr virus (EBV) infection. We named this cell line RM-P1. This cell line showed complex chromosomal abnormalities that could not be identified by G-banding. However, spectral karyotyping analysis determined the origin and organization of all unidentified chromosomal abnormalities. When inoculated into the peritoneal cavity of 8 severe combined immunodeficiency (SCID) mice depleted of natural killer cells, RM-P1 cells induced solid tumor with ascites in all animals tested. These tumor and ascitic cells had the same immunogenotypic features as those of the original RM-P1. These 2 types of cells were positive for both HHV-8 and EBV as demonstrated using polymerase chain reaction. Fluorescence-activated cell sorting analyses showed that neither tumors nor ascitic cells grown in SCID mice expressed leukocyte function-associated antigen (LFA)-1alpha (CD11a), LFA-1lbeta (CD18), LFA-2 (CD2), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-2 (CD102), ICAM-3 (CD50), or leukocyte endothelial adhesion molecule (LECAM)-1 (CD62L), suggesting that these cytoadhesion molecules are not involved in tumor formation of RM-P1 cells in vivo. The establishment of the RM-P1 cell line and the animal model of PEL may provide insights for understanding the relationship between these viruses and PEL and for understand the mechanism for PEL.
 ...
PMID:Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth system using SCID mice. 1221 16


1 2 3 4 Next >>