Previous Fora / 2003
Speakers
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Professor Hans Wigzell |
| Rector The Karolinska Institute Sweden |
Prof. Hans Wigzell is President and Professor of Immunology at the Karolinska Institute, Sweden. In March of 1999 Prof. Wigzell was named scientific adviser to the government by Sweden's Prime Minister Gšran Persson. Prof. Wigzell has been Principal of Karolinska Institute since 1 July 1995, and has been a professor of immunology since 1981. He has been a member of the Nobel Assembly since 1984 and chaired the Nobel Prize Committee from 1990 to 1992. Prof. Wigzell was previously active as Director General for SBL/The Swedish Institute for Infectious Disease Control. Professor Hans Wigzell is the Chairman of the SSES board.
Prof. Wigzell was Professor of Immunology, Uppsala University from 1972 to 1982 and General Director of the Swedish Institute for Infectious Disease Control from 1986 to 1991. He has received numerous prestigious scientific prizes and awards, such as Anders Jahre's Award from Oslo University, Erik Fernstršm Award from Uppsala University and the San Marino Scientific Award. Prof. Wigzell has an Honorary Doctorate from the University of Tor Vergata, Rome and is also a member of the Swedish Royal Academy of Sciences, the Academy of Engineering Sciences, the American Academy of Science, the Danish Academy of Science and the Finnish Academy of Sciences. He is a lifelong Honorary Member of the American Association of Immunologists, a member of the European Molecular Biology Organization (EMBO) and also Academia Europea.
Prof. Wigzell has been the Chief Scientific Advisor to the Swedish Prime Minister since 1999, Chairman of WHO-UNAIDS HIV-vaccine committee and a member of EU-commissioner P. Busquin's European Life Science Group. Hans Wigzell is serving on a number of Editorial Boards and Scientific Advisory Boards, and has authored more than 560 papers in international journals. Prof. Wigzell's main research interests are medicine, pathology, and immunology, with emphasis on topics such as the regulation of antibody synthesis and of transplantation immunity, describing and analyzing components of the immune system, immunity in the maternal-foetal context, immunity in relation to HIV and other infections, DNA as a tool in diagnosis and gene analysis.
As president of the Karolinska Institute, Prof. Wigzell has worked to restructure its workings to foster horizontal collaboration between academia and clinical research. The goal has been to aim research towards efficacy and performance without stamping out "curiosity driven research". In an interview with Frontline (Vol. 18, Issue 8, Apr. 14-17 2001), Professor Wigzell stated "The global trend is towards application-oriented research. This... would kill curiosity-driven research, the basis of several crucial discoveries,". In addition to making significant contributions in medical research, Prof. Wigzell has maintained and active role in the international community; sharing his research and promoting collaboration. It is clear he will greatly contribute to the discussion of Knowledge and Quality of Life.
Resources on the Web
The Karolinska Institute:
http://info.ki.se/index_en.html
The Hans Wigzell Group:
http://www.mtc.ki.se/groups/wigzell/index.htm
The Hans Wigzell Group Publications 2000-2001
http://www.mtc.ki.se/groups/wigzell/publications.htm
Press Release WHO/UNAIDS 21 February 2000WHO AND UNAIDS
JOIN FORCES TO LAUNCH HIV VACCINE INITIATIVE
http://www.who.int/inf-pr-2000/en/pr2000-UNAIDS1.html
UNAIDS:
http://www.unaids.org/
Biovitrum:
http://www.noonanrusso.com/news/view_newsitem.aspx?ItemID=3
Books
P. Perlmann and H. Wigzell, editors. Vaccines. Berlin; ĘNew York: ĘSpringer,Ęc1999. P. Perlmann and H. Wigzell, editors. Malaria Immunology. Basel; New York :Karger, 1988.
Articles
BANDHOLTZ, L.; KREUGER, M. R.; SVANHOLM, C.; WIGZELL, H.; ROTTENGERG, M. E. Adjuvant modulation of the immune responses and the outcome of infection with Chlamydia pneumoniae. Clinical & Experimental Immunology, Dec 2002, Vol. 130 Issue 3, p393, 11p
Abstract: Immunization with different adjuvants resulted in antithetic outcomes of infection with Chlamydia pneumoniae. Immunization with the outer major protein-2 from C. pneumoniae (OMP-2) emulsified in Freund's complete adjuvant (FCA) thus increased the susceptibility of mice to infection with the bacteria. The detrimental effect was not observed upon inoculation of irrelevant antigens or major outer membrane protein (MOMP) in FCA, but was also observed after immunization with FCA-chlamydial heat shock protein-60 (HSP-60). The harmful effect of FCA-OMP-2 depended on the presence of both CD4[sup +] and CD8[sup +] cells and was mediated by IL-10, as shown using gene-ablated mice. The increased susceptibility to infection caused by FCA-OMP-2 immunization was long-lasting and observed in mice infected 4 months after the last dose of immunogen. In contrast, partial protection against C. pneumoniae was observed when FCA was replaced with oligodeoxynucleotides containing immunostimulatory CpG motifs mixed with Freund's incomplete adjuvant (FIA-IS-CpG). These polar outcomes of infection related to the cytokine pattern: antigen-stimulated spleen cells from FCA-OMP-2-immunized mice showed higher IL-10/IFN-? ratios than FIA-IS-CpG-OMP-2-immunized animals. In agreement, sera from FCA-OMP-2 showed higher anti-OMP-2 IgG1/IgG2a ratios than FIA-IS-CpG-OMP-2immunized animals. Finally, OMP-2 also generated a protective response when delivered by a eukaryotic expression vector in tandem with CTLA4, a procedure that targeted OMP-2 to antigen-presenting cells.[ABSTRACT FROM AUTHOR]
Wigzell, Hans. Framework Programmes Evolve. Science, 01/18/2002, Vol. 295 Issue 5554, p443, 2p
Abstract: Focuses on the application of Framework Programs for the creation of European Research Arena on countries in the European Union. Aims of the programs; Description of the Framework Programs by academic scientists; Purpose of the European Research Council.
Katchar, K.; Osorio, L.; Conradi, S.; Wigzell, H.; Gigliotti, D. Disturbances in the Peripheral T-Cell Repertoire of Patients with Motor Neuron Disease: High Levels of Activation and Indirect Evidence of Superantigen. Scandinavian Journal of Immunology, Jul/Aug2001, Vol. 54 Issue 1/2, p220, 5p
Abstract: Our data on peripheral blood T cells from Motor neuron disease (MND) patients indicate major immunological disturbances linkedto this disease. Both CD4[sup +] and CD8[sup +] T-cell subsets displayan increased activity in both populations. Likewise, an increased numberof T-cell expansions were noted in MND patients compared to controls,most dramatically observed in the CD4[sup +] T-cell subset, where 5/144T-cell V genes analyzed in eight subjects turned out to be expanded inthe peripheral blood. In the CD8[sup +] T-cell subset, four out of eight MND patients had peripheral BV gene expansions, 9/144 V genes analyzed. However, the most interesting result was the observation that in three out eight MND patients, expansions concerning the same BV gene were present in both CD4[sup +] and CD8[sup +] subsets (BV8S1 in two and BV12S1 in one patient). Parallel expansions of BV-gene restricted populations in both CD4[sup +] and CD8[sup +] subsets in the same individual, in an major histocompatibility complex (MHC)-unrestricted manner, are normally limited to situations where superantigens are involved. No known superantigen has to date been described with the capacity to simultaneously stimulate both BV8S1, suggesting that the postulated 'MND-associated' superantigen is a hitherto undefined molecule.[ABSTRACT FROM AUTHOR]
Wahlstrom J*, Gigliotti D, Roquet A, Wigzell H, Eklund A, Grunewald J. T cell receptor Vbeta expression in patients with allergic asthma before and after repeated low-dose allergen inhalation. Clin Immunol. 2001 Jul;100(1):31-9.
Caligiuri G, Rottenberg M, Nicoletti A, Wigzell H, Hansson GK. Chlamydia pneumoniae infection does not induce or modify atherosclerosis in mice. Circulation. 2001 Jun 12;103(23):2834-8.
Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, Gudmundsson G. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med. 2001 Feb;7(2):180-5.
Dilara Islam, Lisa Bandholtz, Jakob Nilsson, Hans Wigzell, Birger Christensson, Birgitta Agerberth, Gudmundur H. Gudmundsson. Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator. Nature Medicine 7, 180 - 185 (01 Feb 2001) Article
Summary: Antibacterial peptides are active defense components of innate immunity. Several studies confirm their importance at epithelial surfaces as immediate barrier effectors in preventing infection....
Islam, Dilara; Bandholtz, Lisa; Nilsson, Jakob; Wigzell,Hans; Christensson, Birger; Agerberth, Birgitta; Gudmundsson, Gudmundur H. Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator. Nature Medicine, Feb2001, Vol. 7 Issue 2, p180, 6p
Abstract: Antibacterial peptides are active defense components of innate immunity. Several studies confirm their importance at epithelial surfaces as immediate barrier effectors in preventing infection. Here we report that early in Shigella spp. infections, expression of the antibacterial peptides LL-37 and human ?defensin-1 is reduced or turned off. The downregulation is detected in biopsies from patients with bacillary dysenteries and in Shigella- infected cell cultures of epithelial and monocyte origin. This downregulation of immediate defense effectors might promote bacterial adherence and invasion into host epithelium and could be an important virulence parameter. Analyses of bacterial molecules causing the downregulation indicate Shigella plasmid DNA as one mediator.[ABSTRACT FROM AUTHOR]
Wahlstrom J*, Katchar K, Wigzell H, Olerup O, Eklund A, Grunewald J. Analysis of intracellular cytokines in cd4(+) and cd8(+) lung and blood t cells in sarcoidosis. Am J Respir Crit Care Med. 2001 Jan;163(1):115-21.
Rezvany, Mohammad Reza; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah; Lewin, Nongnit; Avila-Carino, Javier; Osterborg, Anders; Mellstedt, Hankan; Wigzell, Hans. Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia. British Journal of Haematology, Nov2000, Vol. 111 Issue 2, p608, 10p, 5 graphs
Abstract: Summary. This study analysed a naturally occurring specific cellular immunity against tumour cells in chronic lymphocytic leukaemia (CLL) patients. Five out of eight patients had blood T lymphocytes able to recognize spontaneously and specifically the autologous tumour B cells (proliferation assay). In these five patients, detection of cytokines by real-time reverse transcription polymerase chain reaction (RTPCR) revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was the most abundant cytokine gene expressed by the T cells that recognized the autologous tumour B cells. Other activated cytokine genes were ginterferon (IFN), interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha, but not IL-4. This profile suggests a type 1 anti-B-CLL T-cell response. CD80 and CD54 were relatively downregulated on the native tumour B cells compared with control normal B cells. Upregulation of CD80 on the leukaemic cells was mandatory for the induction of such a specific T-cell response. CD80 and CD54 monoclonal antibodies inhibited the specific T-cell DNA synthesis proliferation. The proliferative T-cell response was either MHC class I or class II restricted (inhibition by monoclonal antibodies). The specific cytokine gene expression could be found in isolated CD4, as well as CD8, T-cell subsets. This study demonstrated the presence of a potential natural specific CD4, as well as a CD8 type 1 T-cell immunity against the leukaemic CLL tumour B cells in CLL. A further detailed analysis of the spontaneous anti-CLL T-cell immunity is warranted that may facilitate the development of effective anti-tumour vaccines in CLL.[ABSTRACT FROM AUTHOR]
Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jornvall H, Wigzell H, Gudmundsson GH. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000 Nov 1;96(9):3086-93.
Rezvany, Mohammad Reza; Rabbani, Hodjattallah; Ruden, Ulla; Hammarstrom, Lennart; Wigzell, Hans; Osterborg, Anders; Mellstedt, Hakan. Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia. British Journal of Haematology, Oct2000, Vol. 111 Issue 1, p230, 9p, 1 diagram, 4 graphs
Abstract: Summary. We have previously shown that autologous T cells recognize leukaemic cells from patients with chronic lymphocytic leukaemia (B-CLL) in an MHC class I-and/or II-restricted manner. A candidate recognition structure might be the tumour cell-derived Ig VH complementarity-determining region (CDR)3. Three patients with B-CLL were analysed for the presence of autologous T cells recognizing the tumour-specific VH-CDR3 region. The VH region was shown to be mutated in all three patients. In two patients, a VH-CDR3-specific T-cell response was detected by proliferation assay, as well as by gamma-interferon (IFN) production. The responses could be inhibited by monoclonal antibodies against MHC class II, but not MHC class I. In the third patient, a VH-CDR3 proliferative response was detected, which could be inhibited by an anti-MHC class I monoclonal antibody, but not by anti-MHC class II antibodies. No gamma-IFN response could be detected in this patient. In no patient was an interleukin (IL)-4 response noted. Thus, in patients with B-CLL, naturally occurring T cells recognizing the tumourunique VH-CDR3 region are present.[ABSTRACT FROM AUTHOR]
Rottenberg ME, Gigliotti Rothfuchs A, Gigliotti D, Ceausu M, Une C, Levitsky V, Wigzell H. Regulation and role of IFN-gamma in the innate resistance to infection with Chlamydia pneumoniae. J Immunol. 2000 May 1;164(9):4812-8.
Svanholm C, Bandholtz L, Castanos-Velez E, Wigzell H, Rottenberg ME. Protective DNA immunization against Chlamydia pneumoniae. Scand J Immunol. 2000 Apr;51(4):345-53.
Weissert R, Lobell A*, de Graaf KL, Eltayeb SY, Andersson R, Olsson T, Wigzell H. Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1689-94.
Fernandez-Medina, Daniela; Jansson, Marianne; Rabinovich, Roberto D.; Libonatti, Osvaldo; Wigzell, Hans. Identification of Human Immunodeficiency Virus Type 1 Subtypes B and F, B/F Recombinant and Dual Infection with these Subtypes in Argentina. Scandinavian Journal of Infectious Diseases, Jun99, Vol. 31 Issue 3, p235, 8p, 1 chart, 8 diagrams
Abstract: DNA sequences encoding the third variable region (V3) of human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp120 were obtained from 18 infected individuals residing in different regions of Argentina. Proviral DNA representing the env V3 region was obtained by PCR from uncultured peripheral blood mononuclear cells (PBMC) and genetic heterogeneity was examined by phylogenetic analysis. Sequences representing the gag p17 region were also obtained for a subset of these samples. Moreover, 1 sample that it was not possible to classify according to initial phylogenetic analysis was further analysed by molecular cloning of both V3 and p17 regions. Phylogenetic analysis according to different methodologies were performed comparing obtained sequences with a set of reference sequences representing previously characterized HIV-1 subtypes. The recombinant identification program (RIP) was used to study the presence of possible recombinant sequences. Phylogenetic analysis demonstrated that viruses representing both subtypes B and F are circulating among HIV-1 infected individuals in Argentina. In addition, RIP analysis showed that an initially unclassified sequence exhibited similarities to subtypes B and F in different fragments of the V3 region. Separate phylogenetic analysis of each of these fragments revealed divergent clustering, suggesting that this sequence harbours a point of recombination within the V3 loop. Interestingly, we also identified a dually infected individual with viruses belonging to subtypes B and F, as demonstrated by molecular cloning analysis of the env V3 and the gag p17 regions. Taken together, our study shows that both subtypes B and F are circulating in different regions of Argentina. Moreover, the data presented here show that dual infections with subtypes B and F can occur, and consequently B/F recombinant sequences are arising in the region.[ABSTRACT FROM AUTHOR]
Grunewald, J.; Eklund, A.; Wigzell, H.; Van Meijgaarden, K. E.; Ottenhoff, T. H. M. Bronchoalveolar lavage cells from sarcoidosis patients and healthy controls can efficiently present antigens. Journal of Internal Medicine, Apr99, Vol. 245 Issue 4
Abstract: Objectives: The interaction between antigen-presenting cells (APC) and T lymphocytes, that recognize the antigen-HLA complex using its T cell-receptor for antigen, is of crucial importance for a subsequent specific immune response. In patients with pulmonary sarcoidosis, the local antigen- presenting capacity in the lungs has been suggested to be abnormally enhanced, and implicated in the immunopathogenesis of the disease. This study was aimed at increasing the understanding of the capacity to present antigens by APC in the lung compartment. Design and subjects: We used bronchoalveolar lavage (BAL) cells and paired peripheral blood mononuclear cells (PBMC) of six sarcoidosis patients and two healthy controls to stimulate in total eight well characterized T-cell clones with known HLA and antigen specificities. All subjects were HLA typed. Results.: BAL cells of sarcoidosis patients as well as of healthy controls efficiently induced proliferation of the relevant T-cell clone in an HLA-restricted manner when adding either intact antigen or antigenic peptides. Conclusions.: BAL cells have the capacity to process and present antigens adequately, irrespective of whether they are derived from healthy individuals or from patients with sarcoidosis, implying the alveolar space as an important location for active immune reactions..[ABSTRACT FROM AUTHOR]
Mancia, L.; Wahlstrom, J.; Schiller, B.; Chini, L.; Elinder, G.; D'Argenio, P.; Gigliotti, D.; Wigzell, H.; Rossi, P.; Grunewald, J. Characterization of the T-Cell Receptor V-Beta Repertoire in Kawasaki Disease. Scandinavian Journal of immunology, Oct98, Vol. 48 Issue 4, p443, 7p, 4 charts, 8 graphs
Abstract: Characterizes the T-cell receptor V-beta repertoire in a pediatric multisystem necrotizing vasculitis, the Kawasaki disease (KD). Prevalence of KD among infants and young children; Clinical features; Role of T lymphocytes in acute and convalescent phases of the disease; Immune activation in KD; Implications for the pathogenesis of the disease.
Devito, Claudia; Levi, Michael; Hinkula, Jorma; Medina, R. Daniela Fernandez; Libonatti, Osvaldo; Wigzell, Hans. Seroreactivity to HIV-1 V3 subtypes A to H peptides of Argentinian HIV-positive sera. Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology, Feb98, Vol. 17 Issue 2, p156, 4p, 2 charts
Abstract: Presents a study which tested serum samples from Argentinian human immunodeficiency virus (HIV) patients against a panel of peptides which represented V3 consensus subtypes A through H. Information on the materials and methodology of the study; What the study found; Discussion on the findings of the study.
Wigzell, Hans. The immune system as a therapeutic agent. Scientific American, Sep93, Vol. 269 Issue 3, p126, 8p, 8c, 1bw
Abstract: Explains the therapeutic use of a controlled immune system response. Treatment of cancer; Attack on other pathogens;
Tolerance to transplanted tissues; Control of autoimmune diseases.
Pezzella, M.; Rossi, P.; Lombardi, V.; Gemelli, V.; Costantini, R. Mariani; Mirolo, M.; Fundaro, C.; Moschese, V.; Wigzell, H. HIV viral sequences in seronegative people at risk detected by in situhybridisation and polymerase chain reaction. BMJ: British Medical Journal, 3/18/89, Vol. 298 Issue 6675, p713, 4p, 1 chart, 2bw
Abstract: Assesses the occurrence of infection with human immunodeficiency virus (HIV) among seronegative people in Rome, Italy. Confirmation of HIV genomic sequences using polymerase chain reaction technique; Detection of HIV retroviral sequences by in situ hybridization in peripheral blood mononuclear cells; Analysis of free antigen in the serum by antigen capture assay.