Scholars@Duke
Dhavalkumar Dhirajlal Patel

Dhavalkumar Dhirajlal Patel

Associate Consulting Professor in the Department of Medicine
Medicine, Rheumatology and Immunology
patel003@mc.duke.edu
Duke Box 2632, Durham, NC 27710
University of NC At Chapel Hil, CB# 7280 3330 Thurston Buildin, Chapel Hill, NC 27599-7280

Selected Publications

Toll-like receptor 4 (TLR4)-deficient murine macrophage cell line as an in vitro assay system to show TLR4-independent signaling of Bacteroides fragilis lipopolysaccharide.

Journal Article Infect Immun · September 2002 Bacterial lipopolysaccharides (LPS) activate cells of innate immunity, such as macrophages, by stimulating signaling through toll-like receptor 4 (TLR4). We and others have hypothesized that LPS derived from different bacterial species may function through ... Full text Link to item Cite

Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue.

Journal Article Proc Natl Acad Sci U S A · June 11, 2002 Cowpox virus (Brighton Red strain) possesses one of the largest genomes in the Orthopoxvirus genus. Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is th ... Full text Link to item Cite

CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion.

Journal Article J Biol Chem · May 31, 2002 Featured Publication Fractalkine is a unique CX(3)C chemokine/mucin hybrid molecule that functions like selectins in inducing the capture of receptor-expressing cells. Because of the importance of tyrosine sulfation for ligand binding of the selectin ligand PSGL1, we tested th ... Full text Link to item Cite

Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV.

Journal Article J Biol Chem · May 31, 2002 Human adenosine deaminase (ADA) occurs as a 41-kDa soluble monomer in all cells. On epithelia and lymphoid cells of humans, but not mice, ADA also occurs bound to the membrane glycoprotein CD26/dipeptidyl peptidase IV. This "ecto-ADA" has been postulated t ... Full text Link to item Cite

Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice.

Journal Article Proc Natl Acad Sci U S A · May 28, 2002 Featured Publication Lymphocyte chemotaxis is a complex process by which cells move within tissues and across barriers such as vascular endothelium and is usually stimulated by chemokines such as stromal cell-derived factor-1 (CXCL12) acting via G protein-coupled receptors. Be ... Full text Open Access Link to item Cite

Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival.

Journal Article Blood · February 1, 2002 All genetic types of severe combined immunodeficiency (SCID) can be cured by stem cell transplantation from related donors. The survival rate approaches 80%, and most deaths result from opportunistic infections acquired before transplantation. It was hypot ... Full text Link to item Cite

Mutational analysis of the fractalkine chemokine domain. Basic amino acid residues differentially contribute to CX3CR1 binding, signaling, and cell adhesion.

Journal Article J Biol Chem · June 15, 2001 Featured Publication Fractalkine (FKN/CX3CL1) is a unique member of the chemokine gene family and contains a chemokine domain (CD), a mucin-like stalk, a single transmembrane region, and a short intracellular C terminus. This structural distinction affords FKN the property of ... Full text Link to item Cite

Chemokines have diverse abilities to form solid phase gradients.

Journal Article Clin Immunol · April 2001 Chemokines play critical roles in leukocyte recruitment into sites of inflammation such as rheumatoid arthritis (RA). While chemokines immobilized on endothelium (solid-phase), but not soluble chemokines, direct rolling leukocytes to firmly adhere to endot ... Full text Link to item Cite

Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs.

Journal Article J Clin Invest · March 2001 Recent reports indicate that genes with tissue-restricted expression, including those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512), are transcribed in the t ... Full text Link to item Cite

Comparison of thymocyte development and cytokine production in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient mice.

Journal Article Int Immunol · February 2001 CD7 and CD28 are Ig superfamily molecules expressed on thymocytes and mature T cells that share common signaling 0mechanisms and are co-mitogens for T cell activation. CD7-deficient mice are resistant to lipopolysaccharide (LPS)-induced shock syndrome, and ... Full text Link to item Cite

CXCR3 and CCR5 ligands in rheumatoid arthritis synovium.

Journal Article Clin Immunol · January 2001 The pathogenesis of rheumatoid arthritis (RA) may be mediated by Th1-type T cells. Since chemokine receptors CXCR3 and CCR5 are preferentially expressed on Th1 cells, we tested the expression and regulation of several chemokines, including those that signa ... Full text Link to item Cite

The development of clinical signs of rheumatoid synovial inflammation is associated with increased synthesis of the chemokine CXCL8 (interleukin-8).

Journal Article Arthritis Res · 2001 Paired synovial tissue samples were obtained from both clinically uninvolved (CU) and clinically involved (CI) knee joints of eight rheumatoid arthritis (RA) patients. In addition, biopsies were taken from five control subjects. We observed the expression ... Full text Link to item Cite

T-Cell recovery in adults and children following umbilical cord blood transplantation.

Journal Article Biol Blood Marrow Transplant · 2001 T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated withi ... Full text Link to item Cite

Leukocyte homing to synovium.

Journal Article Curr Dir Autoimmun · 2001 Full text Link to item Cite

Chemokine production by G protein-coupled receptor activation in a human mast cell line: roles of extracellular signal-regulated kinase and NFAT.

Journal Article J Immunol · December 15, 2000 Chemoattractants are thought to be the first mediators generated at sites of bacterial infection. We hypothesized that signaling through G protein-coupled chemoattractant receptors may stimulate cytokine production. To test this hypothesis, a human mast ce ... Full text Link to item Cite

A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.

Journal Article J Immunol · December 1, 2000 The hallmark of acute allograft rejection is infiltration of the inflamed graft by circulating leukocytes. We studied the role of fractalkine (FKN) and its receptor, CX(3)CR1, in allograft rejection. FKN expression was negligible in nonrejecting cardiac is ... Full text Link to item Cite

The binding site of human adenosine deaminase for CD26/Dipeptidyl peptidase IV: the Arg142Gln mutation impairs binding to cd26 but does not cause immune deficiency.

Journal Article J Exp Med · November 6, 2000 Human, but not murine, adenosine deaminase (ADA) forms a complex with the cell membrane protein CD26/dipeptidyl peptidase IV. CD26-bound ADA has been postulated to regulate extracellular adenosine levels and to modulate the costimulatory function of CD26 o ... Full text Link to item Cite

Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis.

Journal Article Proc Natl Acad Sci U S A · August 29, 2000 To identify the physiological functions of the retinoid-related orphan receptor gamma (RORgamma), a member of the nuclear receptor superfamily, mice deficient in RORgamma function were generated by targeted disruption. RORgamma(-/-) mice lack peripheral an ... Full text Link to item Cite

Expression of the human poliovirus receptor/CD155 gene during development of the central nervous system: implications for the pathogenesis of poliomyelitis.

Journal Article Virology · August 1, 2000 The gene for the human poliovirus receptor (hPVR/CD155) is the founding member of a new family of genes encoding proteins belonging to the immunoglobulin superfamily. To determine whether CD155 is expressed during mammalian development, we have made use of ... Full text Link to item Cite

Linkage of the CCR5 Delta 32 mutation with a functional polymorphism of CD45RA.

Journal Article J Immunol · July 1, 2000 A 32-bp deletion in CCR5 (CCR5 Delta 32) confers to PBMC resistance to HIV-1 isolates that use CCR5 as a coreceptor. To study this mutation in T cell development, we have screened 571 human thymus tissues for the mutation. We identified 72 thymuses (12.6%) ... Full text Link to item Cite

Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency.

Journal Article N Engl J Med · May 4, 2000 Featured Publication BACKGROUND: Immune function can be restored in infants with severe combined immunodeficiency by transplantation of unfractionated bone marrow from HLA-identical donors or T-cell-depleted marrow stem cells from haploidentical donors, with whom there is a si ... Full text Link to item Cite

Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy.

Journal Article J Immunol · February 15, 2000 The roles that thymus cytokines might play in regulating thymic atrophy are not known. Reversing thymic atrophy is important for immune reconstitution in adults. We have studied cytokine mRNA steady-state levels in 45 normal human (aged 3 days to 78 years) ... Full text Link to item Cite

Ultrastructure and function of the fractalkine mucin domain in CX(3)C chemokine domain presentation.

Journal Article J Biol Chem · February 11, 2000 Featured Publication Fractalkine (FKN), a CX(3)C chemokine/mucin hybrid molecule on endothelium, functions as an adhesion molecule to capture and induce firm adhesion of a subset of leukocytes in a selectin- and integrin-independent manner. We hypothesized that the FKN mucin d ... Full text Link to item Cite

CD6.

Journal Article J Biol Regul Homeost Agents · 2000 Link to item Cite

The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection.

Journal Article Annu Rev Immunol · 2000 The human thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants a ... Full text Link to item Cite

Resistance of CD7-deficient mice to lipopolysaccharide-induced shock syndromes.

Journal Article J Exp Med · March 15, 1999 CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-gamma production and CD8(+) CTL genera ... Full text Link to item Cite

A 43-nucleotide RNA cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA.

Journal Article Virology · March 1, 1999 The 3' ends of late mRNAs of the ati gene, encoding the major component of the A-type inclusions, are generated by endoribonucleolytic cleavage at a specific site in the primary transcript [Antczak et al., (1992), Proc. Natl. Acad. Sci. USA 89, 12033-12037 ... Full text Link to item Cite

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.

Journal Article J Clin Invest · February 1999 A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we ... Full text Link to item Cite

Cytokine-regulated expression of activated leukocyte cell adhesion molecule (CD166) on monocyte-lineage cells and in rheumatoid arthritis synovium.

Journal Article Arthritis Rheum · December 1998 OBJECTIVE: To determine whether monocyte/macrophage expression of the CD6 ligand, activated leukocyte cell adhesion molecule (ALCAM) (CD166), is regulated by cytokines during inflammation in rheumatoid arthritis (RA). METHODS: We used flow cytometry to tes ... Full text Link to item Cite

Developmental regulation of lymphocyte-specific protein 1 (LSP1) expression in thymus during human T-cell maturation.

Journal Article Hybridoma · December 1998 The lymphocyte specific protein 1 (LSP1) phosphoprotein is an F-actin binding molecule restricted to cells of hematopoietic origin in mice and humans. LSP1 is localized to the internal surface of the plasma membrane, the cytoplasm, and NP-40-insoluble acti ... Full text Link to item Cite

Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow.

Journal Article J Exp Med · October 19, 1998 Featured Publication Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular in ... Full text Link to item Cite

Oxidized alpha2-macroglobulin (alpha2M) differentially regulates receptor binding by cytokines/growth factors: implications for tissue injury and repair mechanisms in inflammation.

Journal Article J Immunol · October 15, 1998 Alpha2M binds specifically to TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, basic fibroblast growth factor (bFGF), beta-nerve growth factor (beta-NGF), platelet-derived growth factor (PDGF), and TGF-beta. Since many of these cytokines are released along with neut ... Link to item Cite

New surrogate markers for autoimmune disease activity.

Journal Article J Clin Invest · September 15, 1998 Full text Link to item Cite

Immunologic characterization of CD7-deficient mice.

Journal Article J Immunol · June 15, 1998 Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid development and function, the exact function of CD7 in vivo has remained elusive. One patient has ... Link to item Cite

CD34+CD38-lin- cord blood cells develop into dendritic cells in human thymic stromal monolayers and thymic nodules.

Journal Article J Immunol · April 1, 1998 Thymic dendritic cells (DCs) appear to have distinct biologic and functional properties compared with DCs in other tissues. Currently, little is known about human thymic DCs because they have been difficult to isolate and culture in vitro. Here, we report ... Link to item Cite

Thymocytes and cultured thymic epithelial cells express transcripts encoding alpha-3, alpha-5 and beta-4 subunits of neuronal nicotinic acetylcholine receptors: preferential transcription of the alpha-3 and beta-4 genes by immature CD4 + 8 + thymocytes.

Journal Article J Neuroimmunol · November 1997 Thymic tissues express transcripts encoding the alpha-3, alpha-5 and beta-4 subunits of nicotinic neuronal acetylcholine receptors (AcChRs) suggesting that neuronal AcChRs similar to those expressed in ganglia are expressed in the thymus. Transcription occ ... Full text Link to item Cite

CD6-ligand interactions: a paradigm for SRCR domain function?

Journal Article Immunol Today · October 1997 The scavenger receptor cysteine-rich (SRCR) superfamily, which includes proteins expressed by leukocytes, can be subdivided into groups A and B. Group B contains the lymphocyte cell-surface receptor CD6. This article reviews recent progress in understandin ... Full text Link to item Cite

Expression of CD44 and variant isoforms in cultured human retinal pigment epithelial cells.

Journal Article Invest Ophthalmol Vis Sci · September 1997 PURPOSE: CD44 is a major hyaluronic acid receptor that exists as a number of isoforms, generated by alternative splicing of 9 "variant" exons in humans (v2 to v10) and 10 exons in rodents. Little is known about the expression and function of CD44 in human ... Link to item Cite

The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes.

Journal Article Nat Genet · March 1997 Featured Publication Type 1, or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease associated with loss of tolerance to several pancreatic islet cell molecules, including insulin, glutamic acid decarboxylase (GAD), ICA69 and the tyrosine phosphatase IA-2 (refs ... Full text Link to item Cite

Arthritis syndromes associated with human T cell lymphotropic virus type I infection.

Journal Article Med Clin North Am · January 1997 Arthritis syndromes occur associated with HTLV-I infection both in the presence and in the absence of clinical ATL, and polyarthritis may be the presenting manifestation of HTLV-I-associated ATL. In both clinical settings, HTLV-I-infected T cells home to a ... Full text Link to item Cite

Functional association of CD7 with phosphatidylinositol 3-kinase: interaction via a YEDM motif.

Journal Article Int Immunol · August 1996 Human CD7 is a 40 kDa protein expressed on thymocytes, early T, B, NK and myeloid lineage cells in bone marrow, and on mature T and NK cells. Previous studies suggested human CD7 may be involved in T and NK cell activation and/or adhesion, and that CD7-med ... Full text Link to item Cite

A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency.

Journal Article Immunity · May 1996 Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but s ... Full text Link to item Cite

Distribution of CD44 variant isoforms in human skin: differential expression in components of benign and malignant epithelia.

Journal Article J Cutan Pathol · December 1995 Expression of cell adhesion molecules regulates epithelial cell differentiation and organization of complex tissues such as skin. The CD44 family of adhesion molecules is generated by alternative splicing of up to 10 variant exons encoding inserts into the ... Full text Link to item Cite

Characterization of human CD7 transgenic mice.

Journal Article J Immunol · September 1, 1995 CD7 is a 40-kDa transmembrane glycoprotein member of the lg gene superfamily expressed on most peripheral blood T lymphocytes and NK cells. CD7 is also expressed on myeloid, NK, B, and T cell precursors during adult hematopoiesis. Because Thy-1 is absent i ... Link to item Cite

Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand.

Journal Article J Exp Med · June 1, 1995 Antibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion. Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 m ... Full text Link to item Cite

Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells.

Journal Article J Exp Med · April 1, 1995 Featured Publication CD6 is a 130-kD glycoprotein expressed on the surface of thymocytes and peripheral blood T cells that is involved in TCR-mediated T cell activation. In thymus, CD6 mediates interactions between thymocytes and thymic epithelial (TE) cells. In indirect immun ... Full text Link to item Cite

Characterization of human thymic epithelial cell surface antigens: phenotypic similarity of thymic epithelial cells to epidermal keratinocytes.

Journal Article J Clin Immunol · March 1995 Cellular interactions between developing thymocytes and cells of the thymic microenvironment are necessary for maturation of thymocytes into mature T cells. While much is known about the molecules on developing T cells that mediate these interactions, litt ... Full text Link to item Cite

AD2, a human molecule involved in the interaction of T cells with epidermal keratinocytes and thymic epithelial cells.

Journal Article J Immunol · March 1, 1995 Interactions between T cells and epithelial cells of the thymus are essential for normal T cell development, and interactions between T cells and skin epidermal keratinocytes occur in the context of inflammatory skin diseases and cutaneous T cell malignanc ... Link to item Cite

Expression of CD44 molecules and CD44 ligands during human thymic fetal development: expression of CD44 isoforms is developmentally regulated.

Journal Article Int Immunol · February 1995 It has recently been recognized that CD44 comprises a large family of alternatively spliced forms. In the thymus, CD44 has been postulated to play an important role in immature T cell migration and maturation. In this paper, we have studied the expression ... Full text Link to item Cite

Physical and genetic linkage of the genes encoding Ly-9 and CD48 on mouse and human chromosomes 1.

Journal Article Immunogenetics · 1995 By virtue of sequence similarity, the genes encoding CD2, CD48, CD58, and Ly-9 have been assigned to a distinct subset within the immunoglobulin superfamily. Previous gene mapping studies in human and mouse have suggested that CD2, CD48, and CD58 arose by ... Full text Link to item Cite

Characterization of a CD6 ligand(s) expressed on human- and murine-derived cell lines and murine lymphoid tissues.

Journal Article Cell Immunol · October 15, 1994 CD6, a type I cell surface glycoprotein expressed predominantly by thymocytes and mature T lymphocytes, becomes phosphorylated on tyrosine residues following T cell activation and has been implicated as an accessory molecule in T cell activation. The purpo ... Full text Link to item Cite

Cell adhesion molecules involved in intrathymic T cell development.

Journal Article Semin Immunol · August 1993 During stem cell migration to the thymus, intrathymic maturation of T cells, and emigration of mature T cells out of the thymus, intercellular interactions of developing T cells with a myriad of cell types are required for normal T cell development. Interc ... Full text Link to item Cite

Site-specific RNA cleavage generates the 3' end of a poxvirus late mRNA.

Journal Article Proc Natl Acad Sci U S A · December 15, 1992 The cowpox virus late mRNAs encoding the major protein of the A-type inclusions have 3' ends corresponding to a single site in the DNA template. The DNA sequence of the Alu I-Xba I fragment at this position encodes an RNA cis-acting signal, designated the ... Full text Link to item Cite

Fine structure mapping and phenotypic analysis of five temperature-sensitive mutations in the second largest subunit of vaccinia virus DNA-dependent RNA polymerase.

Journal Article Virology · January 1990 We have used plasmid clones spanning the region encoding the 132-kDa subunit of the cowpox virus RNA polymerase (CPV rpo 132) to marker rescue each of five vaccinia virus (VV) temperature sensitive (ts) mutants, ts 27, ts 29, ts 32, ts 47, and ts 62, which ... Full text Link to item Cite

The second-largest subunit of the poxvirus RNA polymerase is similar to the corresponding subunits of procaryotic and eucaryotic RNA polymerases.

Journal Article J Virol · March 1989 We have characterized the poxvirus gene encoding the second-largest subunit of the viral DNA-dependent RNA polymerase. This gene, designated rpo132, is located in the HindIII A fragment of the DNA of the Brighton Red strain of cowpox virus. A similar gene ... Full text Link to item Cite

A poxvirus-derived vector that directs high levels of expression of cloned genes in mammalian cells.

Journal Article Proc Natl Acad Sci U S A · December 1988 Featured Publication High levels of expression of cloned genes have been obtained in mammalian cells by using poxvirus-derived insertion/expression vectors. These vectors employ the cis-acting element (CAE I) that directs the transcription of one of the most strongly expressed ... Full text Link to item Cite

Virulence genes of poxviruses and reoviruses.

Journal Article Vaccine · April 1988 Identification of viral genes that specify virulence, however defined, is of critical importance for the design of viral vaccines. In particular, the targeted development not only of avirulent vaccine strains but also of viruses to be used as carriers for ... Full text Link to item Cite

Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences.

Journal Article EMBO J · December 1, 1987 Featured Publication We have identified and characterized one of the most strongly-expressed genes of cowpox virus (CPV). This is the gene encoding the major protein component of the A-type inclusion bodies produced by this virus. This gene (designated the 160K gene) is transc ... Full text Link to item Cite

Isolation of cowpox virus A-type inclusions and characterization of their major protein component.

Journal Article Virology · March 1986 A-type inclusions (ATI)2 are large well-defined structures that appear in the cytoplasm during the late stages of the multiplication cycles of many poxviruses. The ATIs produced by the CPRC1 strain of cowpox virus in strain 143 human osteosarcoma cells hav ... Full text Link to item Cite