David Topham
| Title | Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Microbiology and Immunology in the Center for Vaccine Biology and Immunology |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 609
Rochester NY 14642
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| 2001 |
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| Scholar | Nathan Shock Center for the Study of Aging and Development |
Virus infections of the respiratory tract are responsible for a great deal of illness and even death among the world's human population. Influenza, in particular, has a history of causing deadly pandemics and the continuing emergence of highly pathogenic H5 influenzas around the world is reason for concern. It is essential to understand how the immune system clears a virus infection and provides long term immunity if we are to design more rational vaccination and treatment strategies. The lab has a combined program in basic research using animal models of influenza infection and immunity, as well as a translational research program to study human immune responses to influenza infection and vaccination. Within these programs we are investigating the mechanisms that provide optimal immune protection against influenza virus. One particular focus is to understand how T cells are regulated in the environment of the lung tissue and airways. We believe this is the key to generating long-lived protective immunity against diverse influenza viruses, including potential pandemic strains. The concepts and information we gather from the animal models are being directly translated into the human situation. To this end, we have established the New York Influenza Center of Excellence, a robust, collaborative program for basic and translational investigation of influenza virology, pathogenesis, immunology, and vaccines.
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He XS, Sasaki S, Baer J, Khurana S, Golding H, Treanor JJ, Topham DJ, Sangster MY, Jin H, Dekker CL, Subbarao K, Greenberg HB. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine. J Infect Dis. 2013 Jan; 207(2):288-96.
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Scheible K, Secor-Socha S, Wightman T, Wang H, Mariani TJ, Topham DJ, Pryhuber G, Quataert S. Stability of T cell phenotype and functional assays following heparinized umbilical cord blood collection. Cytometry A. 2012 Nov; 81(11):937-49.
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Guo H, Topham DJ. Multiple Distinct Forms of CD8+ T Cell Cross-Reactivity and Specificities Revealed after 2009 H1N1 Influenza A Virus Infection in Mice. PLoS One. 2012; 7(9):e46166.
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van Helden MJ, van Kooten PJ, Bekker CP, Gröne A, Topham DJ, Easton AJ, Boog CJ, Busch DH, Zaiss DM, Sijts AJ. Pre-existing virus-specific CD8(+) T-cells provide protection against pneumovirus-induced disease in mice. Vaccine. 2012 Oct 5; 30(45):6382-8.
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van Helden MJ, de Graaf N, Boog CJ, Topham DJ, Zaiss DM, Sijts AJ. The bone marrow functions as the central site of proliferation for long-lived NK cells. J Immunol. 2012 Sep 1; 189(5):2333-7.
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Chapman LM, Aggrey AA, Field DJ, Srivastava K, Ture S, Yui K, Topham DJ, Baldwin WM, Morrell CN. Platelets present antigen in the context of MHC class I. J Immunol. 2012 Jul 15; 189(2):916-23.
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Santiago FW, Lambert Emo K, Fitzgerald T, Treanor JJ, Topham DJ. Antigenic and immunogenic properties of recombinant hemagglutinin proteins from H1N1 A/Brisbane/59/07 and B/Florida/04/06 when produced in various protein expression systems. Vaccine. 2012 Jun 29; 30(31):4606-16.
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Li X, Miao H, Henn A, Topham DJ, Wu H, Zand MS, Mosmann TR. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination. Vaccine. 2012 Jun 29; 30(31):4581-4.
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Sundararajan A, Huan L, Richards KA, Marcelin G, Alam S, Joo H, Yang H, Webby RJ, Topham DJ, Sant AJ, Sangster MY. Host differences in influenza-specific CD4 T cell and B cell responses are modulated by viral strain and route of immunization. PLoS One. 2012; 7(3):e34377.
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Santiago FW, Fitzgerald T, Treanor JJ, Topham DJ. Vaccination with drifted variants of avian H5 hemagglutinin protein elicits a broadened antibody response that is protective against challenge with homologous or drifted live H5 influenza virus. Vaccine. 2011 Nov 8; 29(48):8888-97.
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Wu H, Kumar A, Miao H, Holden-Wiltse J, Mosmann TR, Livingstone AM, Belz GT, Perelson AS, Zand MS, Topham DJ. Modeling of influenza-specific CD8+ T cells during the primary response indicates that the spleen is a major source of effectors. J Immunol. 2011 Nov 1; 187(9):4474-82.
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Chapman TJ, Lambert K, Topham DJ. Rapid reactivation of extralymphoid CD4 T cells during secondary infection. PLoS One. 2011; 6(5):e20493.
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de Graaf N, van Helden MJ, Textoris-Taube K, Chiba T, Topham DJ, Kloetzel PM, Zaiss DM, Sijts AJ. PA28 and the proteasome immunosubunits play a central and independent role in the production of MHC class I-binding peptides in vivo. Eur J Immunol. 2011 Apr; 41(4):926-35.
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Azadniv M, Bowers WJ, Topham DJ, Crispe IN. CD4+ T cell effects on CD8+ T cell location defined using bioluminescence. PLoS One. 2011; 6(1):e16222.
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Scheible K, Zhang G, Baer J, Azadniv M, Lambert K, Pryhuber G, Treanor JJ, Topham DJ. CD8+ T cell immunity to 2009 pandemic and seasonal H1N1 influenza viruses. Vaccine. 2011 Mar 3; 29(11):2159-68.
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Mace CR, Topham DJ, Mosmann TR, Quataert SA, Treanor JJ, Miller BL. Label-free, arrayed sensing of immune response to influenza antigens. Talanta. 2011 Jan 15; 83(3):1000-5.
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Guo H, Santiago F, Lambert K, Takimoto T, Topham DJ. T cell-mediated protection against lethal 2009 pandemic H1N1 influenza virus infection in a mouse model. J Virol. 2011 Jan; 85(1):448-55.
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Richards KA, Topham D, Chaves FA, Sant AJ. Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus. J Immunol. 2010 Nov 1; 185(9):4998-5002.
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Guo H, Topham DJ. Interleukin-22 (IL-22) production by pulmonary Natural Killer cells and the potential role of IL-22 during primary influenza virus infection. J Virol. 2010 Aug; 84(15):7750-9.
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Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. J Virol. 2010 Jul; 84(13):6687-98.
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Chapman TJ, Topham DJ. Identification of a unique population of tissue-memory CD4+ T cells in the airways after influenza infection that is dependent on the integrin VLA-1. J Immunol. 2010 Apr 1; 184(7):3841-9.
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Desmet EA, Hollenbaugh JA, Sime PJ, Wright TW, Topham DJ, Sant AJ, Takimoto T, Dewhurst S, Maggirwar SB. Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells. Virology. 2010 May 10; 400(2):224-32.
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Bernard MP, Bancos S, Chapman TJ, Ryan EP, Treanor JJ, Rose RC, Topham DJ, Phipps RP. Chronic inhibition of cyclooxygenase-2 attenuates antibody responses against vaccinia infection. Vaccine. 2010 Feb 3; 28(5):1363-72.
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Baer J, Santiago F, Yang H, Wu H, Holden-Wiltse J, Treanor J, Topham DJ. B cell responses to H5 influenza HA in human subjects vaccinated with a drifted variant. Vaccine. 2010 Jan 22; 28(4):907-15.
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Lee HY, Topham DJ, Park SY, Hollenbaugh J, Treanor J, Mosmann TR, Jin X, Ward BM, Miao H, Holden-Wiltse J, Perelson AS, Zand M, Wu H. Simulation and prediction of the adaptive immune response to influenza A virus infection. J Virol. 2009 Jul; 83(14):7151-65.
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Bancos S, Bernard MP, Topham DJ, Phipps RP. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol. 2009; 258(1):18-28.
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Crompton PD, Mircetic M, Weiss G, Baughman A, Huang CY, Topham DJ, Treanor JJ, Sanz I, Lee FE, Durbin AP, Miura K, Narum DL, Ellis RD, Malkin E, Mullen GE, Miller LH, Martin LB, Pierce SK. The TLR9 ligand CpG promotes the acquisition of Plasmodium falciparum-specific memory B cells in malaria-naive individuals. J Immunol. 2009 Mar 1; 182(5):3318-26.
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Elphick GF, Sarangi PP, Hyun YM, Hollenbaugh JA, Ayala A, Biffl WL, Chung HL, Rezaie AR, McGrath JL, Topham DJ, Reichner JS, Kim M. Recombinant human activated protein C inhibits integrin-mediated neutrophil migration. Blood. 2009 Apr 23; 113(17):4078-85.
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Lin GH, Sedgmen BJ, Moraes TJ, Snell LM, Topham DJ, Watts TH. Endogenous 4-1BB ligand plays a critical role in protection from influenza-induced disease. J Immunol. 2009 Jan 15; 182(2):934-47.
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Kyu SY, Kobie J, Yang H, Zand MS, Topham DJ, Quataert SA, Sanz I, Lee FE. Frequencies of human influenza-specific antibody secreting cells or plasmablasts post vaccination from fresh and frozen peripheral blood mononuclear cells. J Immunol Methods. 2009 Jan 1; 340(1):42-7.
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Borowski AB, Boesteanu AC, Mueller YM, Carafides C, Topham DJ, Altman JD, Jennings SR, Katsikis PD. Memory CD8+ T cells require CD28 costimulation. J Immunol. 2007 Nov 15; 179(10):6494-503.
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Richter MV, Topham DJ. The alpha1beta1 integrin and TNF receptor II protect airway CD8+ effector T cells from apoptosis during influenza infection. J Immunol. 2007 Oct 15; 179(8):5054-63.
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Klein I, Cornejo JC, Polakos NK, John B, Wuensch SA, Topham DJ, Pierce RH, Crispe IN. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood. 2007 Dec 1; 110(12):4077-85.
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Polakos NK, Klein I, Richter MV, Zaiss DM, Giannandrea M, Crispe IN, Topham DJ. Early intrahepatic accumulation of CD8+ T cells provides a source of effectors for nonhepatic immune responses. J Immunol. 2007 Jul 1; 179(1):201-10.
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Richards KA, Chaves FA, Krafcik FR, Topham DJ, Lazarski CA, Sant AJ. Direct ex vivo analyses of HLA-DR1 transgenic mice reveal an exceptionally broad pattern of immunodominance in the primary HLA-DR1-restricted CD4 T-cell response to influenza virus hemagglutinin. J Virol. 2007 Jul; 81(14):7608-19.
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Richter M, Ray SJ, Chapman TJ, Austin SJ, Rebhahn J, Mosmann TR, Gardner H, Kotelianski V, deFougerolles AR, Topham DJ. Collagen distribution and expression of collagen-binding alpha1beta1 (VLA-1) and alpha2beta1 (VLA-2) integrins on CD4 and CD8 T cells during influenza infection. J Immunol. 2007 Apr 1; 178(7):4506-16.
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Kessels HW, Schepers K, van den Boom MD, Topham DJ, Schumacher TN. Generation of T cell help through a MHC class I-restricted TCR. J Immunol. 2006 Jul 15; 177(2):976-82.
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Treanor J, Wu H, Liang H, Topham DJ. Immune responses to vaccinia and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults. Vaccine. 2006 Nov 17; 24(47-48):6913-23.
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Polakos NK, Cornejo JC, Murray DA, Wright KO, Treanor JJ, Crispe IN, Topham DJ, Pierce RH. Kupffer cell-dependent hepatitis occurs during influenza infection. Am J Pathol. 2006 Apr; 168(4):1169-78; quiz 1404-5.
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Topham DJ, Chapman TJ, Richter M. Lymphoid and extralymphoid CD4 T cells that orchestrate the antiviral immune response. Expert Rev Clin Immunol. 2006 Mar; 2(2):267-76.
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Divekar AA, Zaiss DM, Lee FE, Liu D, Topham DJ, Sijts AJ, Mosmann TR. Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells, whereas infections induce more IFN-gamma-secreting cells. J Immunol. 2006 Feb 1; 176(3):1465-73.
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Chapman TJ, Castrucci MR, Padrick RC, Bradley LM, Topham DJ. Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection. Virology. 2005 Sep 30; 340(2):296-306.
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Aronica MA, Swaidani S, Zhang YH, Mitchell D, Mora AL, McCarthy S, O'Neal J, Topham D, Sheller JR, Boothby M. Susceptibility to allergic lung disease regulated by recall responses of dual-receptor memory T cells. J Allergy Clin Immunol. 2004 Dec; 114(6):1441-8.
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Ray SJ, Franki SN, Pierce RH, Dimitrova S, Koteliansky V, Sprague AG, Doherty PC, de Fougerolles AR, Topham DJ. The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity. 2004 Feb; 20(2):167-79.
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Sangster MY, Riberdy JM, Gonzalez M, Topham DJ, Baumgarth N, Doherty PC. An early CD4+ T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T-B interactions. J Exp Med. 2003 Oct 6; 198(7):1011-21.
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Topham DJ, Crispe IN. Contrasting urban and rural lifestyles of memory CD8+ T cells. Immunity. 2003 May; 18(5):584-6.
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Topham DJ, Castrucci MR, Wingo FS, Belz GT, Doherty PC. The role of antigen in the localization of naive, acutely activated, and memory CD8(+) T cells to the lung during influenza pneumonia. J Immunol. 2001 Dec 15; 167(12):6983-90.
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Topham DJ, Cardin RC, Christensen JP, Brooks JW, Belz GT, Doherty PC. Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity. J Gen Virol. 2001 Aug; 82(Pt 8):1971-81.
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Ramamurthy L, Barbour V, Tuckfield A, Clouston DR, Topham D, Cunningham JM, Jane SM. Targeted disruption of the CP2 gene, a member of the NTF family of transcription factors. J Biol Chem. 2001 Mar 16; 276(11):7836-42.
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Sangster MY, Topham DJ, D'Costa S, Cardin RD, Marion TN, Myers LK, Doherty PC. Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. J Immunol. 2000 Feb 15; 164(4):1820-8.
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Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN. SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell. 1999 Sep 3; 98(5):609-16.
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Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999 Sep 3; 98(5):617-27.
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Moriggl R, Sexl V, Piekorz R, Topham D, Ihle JN. Stat5 activation is uniquely associated with cytokine signaling in peripheral T cells. Immunity. 1999 Aug; 11(2):225-30.
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Bunting KD, Galipeau J, Topham D, Benaim E, Sorrentino BP. Effects of retroviral-mediated MDR1 expression on hematopoietic stem cell self-renewal and differentiation in culture. Ann N Y Acad Sci. 1999 Apr 30; 872:125-40; discussion 140-1.
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Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster MY, Bunting KD, Grosveld GC, Ihle JN. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity. 1999 Feb; 10(2):249-59.
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Moriggl R, Marine JC, Topham DJ, Teglund S, Sexl V, McKay C, Piekorz R, Wang D, Parganas E, Yoshimura A, Ihle JN. Differential roles of cytokine signaling during T-cell development. Cold Spring Harb Symp Quant Biol. 1999; 64:389-95.
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Topham DJ, Doherty PC. Longitudinal analysis of the acute Sendai virus-specific CD4+ T cell response and memory. J Immunol. 1998 Nov 1; 161(9):4530-5.
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Brown MP, Topham DJ, Sangster MY, Zhao J, Flynn KJ, Surman SL, Woodland DL, Doherty PC, Farr AG, Pattengale PK, Brenner MK. Thymic lymphoproliferative disease after successful correction of CD40 ligand deficiency by gene transfer in mice. Nat Med. 1998 Nov; 4(11):1253-60.
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Bunting KD, Galipeau J, Topham D, Benaim E, Sorrentino BP. Transduction of murine bone marrow cells with an MDR1 vector enables ex vivo stem cell expansion, but these expanded grafts cause a myeloproliferative syndrome in transplanted mice. Blood. 1998 Oct 1; 92(7):2269-79.
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Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, Vanin EF, Bodner S, Colamonici OR, van Deursen JM, Grosveld G, Ihle JN. Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998 May 1; 93(3):385-95.
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Topham DJ, Doherty PC. Clearance of an influenza A virus by CD4+ T cells is inefficient in the absence of B cells. J Virol. 1998 Jan; 72(1):882-5.
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Topham DJ, Tripp RA, Doherty PC. CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J Immunol. 1997 Dec 1; 159(11):5197-200.
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Doherty PC, Hamilton-Easton AM, Topham DJ, Riberdy J, Brooks JW, Cardin RD. Consequences of viral infections for lymphocyte compartmentalization and homeostasis. Semin Immunol. 1997 Dec; 9(6):365-73.
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Doherty PC, Topham DJ, Tripp RA, Cardin RD, Brooks JW, Stevenson PG. Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections. Immunol Rev. 1997 Oct; 159:105-17.
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Tripp RA, Topham DJ, Watson SR, Doherty PC. Bone marrow can function as a lymphoid organ during a primary immune response under conditions of disrupted lymphocyte trafficking. J Immunol. 1997 Apr 15; 158(8):3716-20.
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Topham DJ, Tripp RA, Hamilton-Easton AM, Sarawar SR, Doherty PC. Quantitative analysis of the influenza virus-specific CD4+ T cell memory in the absence of B cells and Ig. J Immunol. 1996 Oct 1; 157(7):2947-52.
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Bright JJ, Topham DJ, Nag B, Lodge PA, Sriram S. Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE. J Neuroimmunol. 1996 Jul; 67(2):119-24.
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Doherty PC, Topham DJ, Tripp RA. Establishment and persistence of virus-specific CD4+ and CD8+ T cell memory. Immunol Rev. 1996 Apr; 150:23-44.
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Topham DJ, Tripp RA, Sarawar SR, Sangster MY, Doherty PC. Immune CD4+ T cells promote the clearance of influenza virus from major histocompatibility complex class II -/- respiratory epithelium. J Virol. 1996 Feb; 70(2):1288-91.
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Fabry Z, Topham DJ, Fee D, Herlein J, Carlino JA, Hart MN, Sriram S. TGF-beta 2 decreases migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. J Immunol. 1995 Jul 1; 155(1):325-32.
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Ewing C, Topham DJ, Doherty PC. Prevalence and activation phenotype of Sendai virus-specific CD4+ T cells. Virology. 1995 Jun 20; 210(1):179-85.
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Topham DJ, Nag B, Arimilli S, Sriram S. A synthetic peptide from the third hypervariable region of major histocompatibility complex class II beta chain as a vaccine for treatment of experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1994 Aug 16; 91(17):8005-9.
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Sriram S, Topham DJ, Carroll L, Shenoy M, Adesina A, Craighead JE. In vivo administration of TNF-alpha prevents EMC-M virus induced viral encephalitis. Int Immunol. 1991 Jul; 3(7):641-5.
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Topham DJ, Adesina A, Shenoy M, Craighead JE, Sriram S. Indirect role of T cells in development of polioencephalitis and encephalomyelitis induced by encephalomyocarditis virus. J Virol. 1991 Jun; 65(6):3238-45.
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Sriram S, Topham DJ, Huang SK, Rodriguez M. Treatment of encephalomyocarditis virus-induced central nervous system demyelination with monoclonal anti-T-cell antibodies. J Virol. 1989 Oct; 63(10):4242-8.
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Sriram S, Topham DJ, Carroll L. Haplotype-specific suppression of experimental allergic encephalomyelitis with anti-IA antibodies. J Immunol. 1987 Sep 1; 139(5):1485-9.
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