John G. Tew, Ph.D.
Professor

Phone: (804) 828-9715
Dept. Fax: (804) 828-9946
e-mail: tew@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
P.O. Box 980678
1220 E. Marshall St., Medical Sciences Building II Room 4036
Richmond, VA 23298-0678

Professional Experience

• B.S., 1966, Brigham Young University
• M.S., 1967, Brigham Young University
• Ph.D., 1970, Brigham Young University
• Postdoctoral, 1970-1972, Case Western Reserve University

Research Interests:

Our lab focuses on mechanisms involved in regulating the germinal center (GC) reaction where specific antibody responses are designed and refined. Follicular dendritic cells (FDCs) are a major focus of our interest and FDCs are localized to the light zones of GCs, where their dendritic processes interdigitate and form three-dimensional networks or FDC-reticula that help these non-circulating cells remain localized.  FDC functions include the production of chemokines that help organize lymphoid follicles including the GC, capture and retention of immune complexes (ICs), presentation of ICs to B cells under conditions that minimize activation of the immuno tyrosine inhibitory motif, promotion of B cell survival, promotion of Ig class switching, induction of somatic hypermutation to diversify the antibody response, production of high affinity Abs that are biologically active at low concentrations, and B cell selection associated with affinity maturation. Current studies are focusing on somatic hypermutation, which they have been able to set up in culture staring with naïve B cells. Importantly, we are the first to be able to do this and it provides us with an opportunity to study mechanisms promoting somatic hypermutation under controlled conditions in vitro.

By use of Ag bearing FDCs, human CD4 T cells primed by incubation with processed Ag on DCs, and naïve human B cells we have been able to set up germinal center reactions entirely in vitro.  This in vitro primary response switches from IgM in the first week to IgG in the second weak and the responses appears to affinity mature. This human immune system in vitro is being used to study the response of the human to different formulations of Ag and different adjuvants, etc. In another application, the functional in vitro human immune system can be used to study the response to toxic agents and pathogens with human cells without risk of human disease. It is important to appreciate that the functional element of a lymph node is the follicle, which develops a GC when stimulated by antigen. The GC is the "hot spot" in the lymph node where critical interactions take place in developing an effective humoral immune response. Upon antigen stimulation, follicles are replicated and an active human lymph node can have dozens of active follicles with functioning GCs where interactions between B cells, T cells, and FDCs take place. We hope to use this artificial immune system to examine humoral responses to developing vaccines (e.g. “bird flu”).  Thus, the human response may be determined rapidly in vitro resulting in an assessment that minimizes studies in animals and testing in humans.

In another project we are working to better understand why periodontitis patients have increased risk of atherosclerosis. We have found that many patients have extraordinary levels of anti-phospolipids including anti-cardiolipin that promotes the maturation of DCs and the production of high levels of type-1 cytokines from DCs, macrophages, NK cells, and T cells. We are exploring the possibility that these anti-phospholipides, that appear to be induced by periodontitis associated bacteria, increase the risk of atherosclerosis in periodontitis patients. If this proves to be the case, it suggests that dental care may not only save your teeth but may reduce the risk of heart attack and stroke and thus potentially save your life.   

Selected Publications:

Tew, J.G., M.H. Kosco, G.F. Burton and A.K. Szakal. Follicular dendritic cells as accessory cells. Immunological Reviews 117:185-211 (1990).

Tew, J.G., R.M. Dilosa, G.F. Burton, M.H. Kosco, L.I. Kupp, A. Masuda and A.K. Szakal. Germinal centers and antibody production in bone marrow. Immunological Reviews 126:99-112 (1992).

Burton, G.F., D.H. Conrad, A.K. Szakal and J.G. Tew. Follicular dendritic cells (FDC) and B cell Co-stimulation. J. Immunol. 150:31-38 (1993.).

Lu, H., J.V. Califano, H.A. Schenkein and J.G. Tew. Immunoglobulin class and subclass distribution of antibodies reactive with the immunodominant antigen of Actinobacillus actinomycetemcomitans serotype b. Infect. Immun. 61:2400-2407 (1993).

Helm, S.T.L., G.F. Burton, A.K. Szakal and J.G. Tew: Follicular dendritic cells and the maintenance of IgE responses Eur. J. Immunol. 25: 2362-2369, (1995)

Masuda, A., G.F. Burotnh, A.K. Szakal and J.G. Tew: Loss of Follicular dendritic cells (FDC) in Murine Acquired Immunodeficiency Syndrome (MAIDS) Laboratory Invest. 79: 511-520, (1995).

Schenkein, H.A., J.C. Gunsolley, T.E. Koertge, J.G. Schenkein, J.G. Tew: Assessment of the effects of smoking on the extent and severity of early-onset periodontitis. J. Amer. Dent. Assoc. 126:1107-1112, (1995).

Wu, J., D. Qin, G.F. Burton, A.K. Szakal and J.G. Tew: Follicular dendritic cell (FDC) derived Ag and accessory activity in initiation of memory IgG responses in vitro. J. Immunol. 157: 3404-3411 (1996).

Tew, J.G., J. Wu, D. Qin, S. Helm, G.F. Burton, and A.K. Szakal: Follicular dendritic cells and presentation of antigen and costimulatory signals to B cells. Immunological Reviews 156: 39-52 (1997).

Burton, G.F., A.K. Masuda, S.L. Heath, B.A. Smith, J.G. Tew and A.K. Szakal: Follicular dendritic cells (FDC) in retroviral infection: Host pathogen perspectives. Immunological Reviews 156: 185-197 (1997).

Zhang, J.G., S.M. Quinn, M. Rausch, J.C. Gunsolley, H.A. Schenkein and J.G. Tew: Hyperimmunoglobulin G production in localized juvenile periodontitis patients and it's regulation by monocytes. Infect. Immun. 64: 2004-2009 (1996).

Quinn, S.M., J.B. Zhang, J.C. Gunsolley, J.G. Schenkein, H.A. Schenkein and J.G. Tew: The influence of smoking and race on IgG subclass concentrations in early-onset periodontitis patients. Infect. Immun. 64: 2500-2505 (1996).

Califano, J.V., J.C. Gunsolley, K. Nakashima, H.A. Schenkein, M.E. Wilson and J.G. Tew: Influence of anti-Actinobacillus actinomycetemcomitans Y4 (serotype b) LPS on severity of generalized early onset periodontitis. Infect. Immun. 64: 3908-3910 (1996).  

Tew JG, Wu J, Qin D, Helm S, Burton GF, Szakal AK. Follicular dendritic cells and presentation of antigen and costimulatory signals to B cells. Immunol Rev. 1997 Apr;156:39-52. Review.

Califano JV, Gunsolley JC, Schenkein HA, Tew JG. A comparison of IgG antibody reactive with Bacteroides forsythus and Porphyromonas gingivalis in adult and early-onset periodontitis. J Periodontol. 1997 Aug;68(8):734-8.

Nakashima K, Schenkein HA, Califano JV, Tew JG. Heterogeneity of antibodies reactive with the dominant antigen of Actinobacillus actinomycetemcomitans. Infect Immun. 1997 Sep;65(9):3794-8.

Tangada SD, Califano JV, Nakashima K, Quinn SM, Zhang JB, Gunsolley JC, Schenkein, HA, Tew JG.. The effect of smoking on serum IgG2 reactive with Actinobacillus actinomycetemcomitans in early-onset periodontitis patients. J Periodontol. 1997 Sep;68(9):842-50.

Hahn CL, Schenkein HA, Tew JG. Polyclonal B cell activators and in vitro induction of auto-antibody reactive with collagen. J Periodontal Res. 1997 Oct;32(7):608-13.

Quinn SM, Zhang JB, Gunsolley JC, Schenkein HA, Tew JG. The influence of smoking and race on adult periodontitis and serum IgG2 levels. J Periodontol. 1998 Feb;69(2):171-7.

Kapasi ZF, Qin D, Kerr WG, Kosco-Vilbois MH, Shultz LD, Tew JG, Szakal AK. Follicular dendritic cell (FDC) precursors in primary lymphoid tissues. J Immunol. 1998 Feb 1;160(3):1078-84.

Qin D, Wu J, Carroll MC, Burton GF, Szakal AK, Tew JG. Evidence for an important interaction between a complement-derived CD21 ligand on follicular dendritic cells and CD21 on B cells in the initiation of IgG responses. J Immunol. 1998 Nov 1;161(9):4549-54.

Smith JP, Burton GF, Tew JG, Szakal AK. Tingible body macrophages in regulation of germinal center reactions. Dev Immunol.1998;6(3-4):285-94.

Masuda, A., G.F. Burton, B.A. Fuchs, B.S. Bhogal, R. Rupper, A.K. Szakal and J.G. Tew: Follicular dendritic cell function and murine AIDS. Immunology 81: 41-46, 1994.

Lu, H., M. Wang, J.C. Gunsolley, H.A. Schenkein and J.G. Tew: Serum immunoglobulin G. subclass concentrations in periodontally healthy and diseased individuals. Infect. Immun. 62:1677-1682, 1994.

Burton, G.F., Z.F. Kapasi, A.K. Szakal and J.G. Tew: The generation and maintenance of antibody and B cell memory. In: Vaccine Strategies to Control Infections, G.L. Ada, Editor. Landes Company, pp. 35-49, 1994.

Kapasi, Z.F., M.H. Kosco-Vilbois, L.D. Shultz, J.G. Tew and A.K. Szakal: Cellular origin of follicular dendritic cells. Adv. Exp. Med. Biol. 355:231-235, 1994.

Caffrey, R.E, Z.F. Kapasi, S.T. Haley, J.G. Tew and A.K. Szakal: DHEAS enhances germinal center responses in old mice. Adv. Exp. Med. Biol. 355:225-239, 1994.

Maeda, K., M.H. Kosco, G.F. Burton, A.K. Szakal, and J.G. Tew: Expression of the intercellular adhesion molecule-1 (ICAM-1) on HEV and on non-lymphoid antigen handling cells: Interdigitating cells, antigen transport cells, and follicular dendritic cells. Cell Tissue Res. 279:47-54, 1995.

Burton, G.F., L.I. Kupp, E.C. Mcnalley and J.G. Tew: Follicular dendritic cells and B cell chemotaxis. Eur. J. Immunol. 25:1105-1108, 1995.

Tew, J.G., G.F. Burton, S. Helm, J. Wu, D. Qin, E. Hahn, and A.K. Szakal: Murine follicular dendritic cells: Accessory activities in vitro . In Follicular Dendritic Cells. Kosco-Vilbois, M.H. Ed. Springer-Verlag, Heidelberg. 6:93-104, 1995.

Szakal, A.K., Z.F. Kapasi, S.T. Haley and J.G. Tew: A theory of follicular dendritic cell origin. In Follicular Dendritic Cells. Kosco-Vilbois, M.H. Ed. Springer-Verlag, Heidelberg. 6:1-13, 1995.

Haley, S.T., J.G. Tew and A. K. Szakal: The monoclonal antibody FDC-M1 recognizes possible follicular dendritic cell precursors in the blood and bone marrow. Adv. Exp. Med. Biol. 378:289-291, 1995.

Wu, J., D. Qin, G.F. Burton, A.K. Szakal and J.G. Tew: Iccosomes and induction of specific antibody production in vitro . Adv. Exp. Med. Biol. 378:309-311, 1995.

Szakal, A.K., Z.F. Kapasi, S.T. Haley and J.G. Tew: Multiple lines of evidence favoring a bone marrow derivation of follicular dendritic cells (FDC). Adv. Exp. Med. Biol. 378:267-272, 1995.

Schenkein, H.A., J.C. Gunsolley, T.E. Koertge, J.G. Schenkein and J. G. Tew: Assessment of the effects of smoking on the extent and severity of early-onset periodontitis. J. Amer. Dent. Assoc. 126:1107-1112, 1995.

Kapasi, Z.F., S.T. Haley, J.G. Tew and A.K. Szakal: Origin of follicular dendritic cells, In: Follicular Dendritic Cells, Earnst Heinen Editor. Karger-Varlag, Basel, Switzerland. pp. 23-30, 1995.

Masuda, A., G.F. Burton, A.K. Szakal and J.G. Tew: Loss of Follicular dendritic cells (FDC) in murine acquired immunodeficiency syndrome (MAIDS). Laboratory Invest. 79:511-520, 1995

Helm, S.T.L., G.F. Burton, A.K. Szakal and J.G. Tew: Follicular dendritic cells and the maintenance of IgE responses Eur. J. Immunol. 25:2362-2369, 1995.

Heath, S.L., J.G. Tew, A.K. Szakal and G.F. Burton: Follicular dendritic cells and human immunodeficiency virus infectivity. Nature 377:740-744, 1995.

Schenkein, H.A., J.C. Gunsolley, T.E. Koertge, J.G. Schenkein and J.G. Tew: Rauchen und die auswirkung auf früh beginnende parodontitis. Phillip Journal 126:381-385, 1996.

Tew, J.G., G.F. Burton and A.K. Szakal: Accessory cells in antibody responses. In Handbook of Experimental Immunology, The Lymphoid System Antibody Responses and affinity maturation, Sir G.J.V. Nossal Editor (Volume 3 Chapter 90) Rockwell Scientific Publications, Oxford, 1996.

Tew, J.G., J.B. Zhang, S. Quinn, S. Tangata, K. Nakashima, J. Gunsoley, H. Schenkein and J. Califano. Antibody of the IgG2 subclass, Actinobacillus actinomycetemocmitans and early-onset periodontitis. J. Periodontol. 67:317-322, 1996.

Marazita, M.L., H. Lu, M.E. Cooper, S.M. Quin, J. Zhang, J.A. Burmeister, J.V. Califano, J.P. Pandey, H.A. Schenkein and J.G. Tew: Genetic segregation analyses of serum IgG2 levels. Am. J. Hum. Gen. 58:1042-1049, 1996.

Zhang, J.G., S.M. Quinn, M. Rausch, J.C. Gunsolley, H.A. Schenkein and J.G. Tew: Hyper-immunoglobulin G production in localized juvenile periodontitis patients and it's regulation by monocytes. Infect. Immun. 64:2004-2009, 1996.

Quinn, S.M., J.B. Zhang, J.C. Gunsolley, J.G. Schenkein, H.A. Schenkein and J.G. Tew: The influence of smoking and race on IgG subclass concentrations in early-onset periodontitis patients. Infect. Immun. 64:2500-2505, 1996.

Califano, J.V., J.C. Gunsolley, K. Nakashima, H.A. Schenkein, M.E. Wilson and J.G. Tew: Influence of anti- Actinobacillus actinomycetemcomitans Y4 (serotype b) LPS on severity of generalized early onset periodontitis. Infect. Immun. 64:3908-3910, 1996.

Wu, J., D. Qin, G.F. Burton, A.K. Szakal and J.G. Tew: Follicular dendritic cell (FDC) derived Ag and accessory activity in initiation of memory IgG responses in vitro . J. Immunol. 157:3404-3411, 1996.

Califano, J., B. Pace, J. Gunsolley, H. Schenkein, L. Lally and J.G. Tew: Antibody reactive with Actinobacillus Actinomycetemocmitans in early cellinteractions. Adv. Exp. Med. Biol. 417:493-497, 1997. onset periodontitis patients. Oral Microbiol. Immunol. 12:20-26, 1997.

Qin, D., J. Wu, G.F. Burton, A.K. Szakal and J.G. Tew: A role for CR2 in FDC-B cellinteractions. Adv. Exp. Med. Biol. 417:493-497, 1997.

Tew, J.G., J. Wu, D. Qin, S. Helm, G.F. Burton, and A.K. Szakal: Follicular dendritic cells and presentation of antigen and costimulatory signals to B cells. Immunological Reviews 156:39-52, 1997.

Burton, G.F., A.K. Masuda, S.L. Heath, B.A. Smith, J.G. Tew and A.K. Szakal: Follicular dendritic cells (FDC) in retroviral infection: Host pathogen perspectives. Immunological Reviews 156:185-197, 1997.

Pandey, J.P., J.C. Gunsolley, J.G. Tew and H.A. Schenkein: GM allotypes and IgG subclass concentrations in blacks. Exp. Clin. Immunogenetics 13:126- 130, 1997.

Barbour, S.E., K. Nakashima, J.B. Zhang, S. Tangada, C.L. Hahn, H.A. Schenkein and J.G. Tew: Tobacco and smoking: environmental factors that modify the host response (Immune System) and impact on periodontal Health. CRC Crit. Rev. Oral Biol. 8:437-460, 1997.

Gunsolley, J.C. Pandey, J.G. Tew, Quinn, S.M. and H.A. Schenkein: The Effect of race, smoking and immunoglobulin allotypes on IgG subclass concentrations. J. Perio. Res. 32:381-387, 1997.

Gunsolley, J.C., Quinn, S.M., Tew, J.G., Schenkein, H.A. The effect of smoking on subjects with minimal periodontal destruction. J. Periodontol. 69:165-170, 1997.

Tangada, S.D., J.V. Califano, K. Nakashima, S.M. Quinn, J.B. Zhang, J.C. Gunsolley, H.A.Schenkein and J.G. Tew: The effect of smoking on serum IgG2 reactive with Actinobiacillus Actinomycetemcomitans in early-onset periodontitis patients. J. Periodontol. 68:842-850, 1997.

Nakashima, K., H.A. Schenkein, J.V. Califano and J.G. Tew: Heterogeneity of antibodies reactive with the dominant antigen of Actinobiacillus Actinomycetemcomitans . Infect. Immun. 65:3794-3798, 1997.

Hahn, E., H.A. Schenkein and J.G. Tew: Polyclonal B cell activators and in vitro induc- tion of auto-antibody reactive with collagen. J. Perio. Res. 32:608-613, 1997.

Quinn, S.M., J.B. Zhang, J.C. Gunsolley, J.G. Schenkein, H.A. Schenkein and J.G. Tew: The influence of smoking and race on adult periodontitis and serum IgG2 levels. J. Periodontol. 69:171-177, 1998.

Smith, J.P., J.G. Tew and A.K. Szakal: Tingible body macrophages, prostaglandins, and germinal centers. Devel. Immunol.6:285-294, 1998.

Tew, J.G., Z. Kapasi, D. Qin, and A.K. Szakal: Origin of Follicular Dendritic Cells. In: "Dendritic Cells: Biology and Clinical Applications." Lotze, M. and A. Thomson, Editors. Academic Press, London. Chapter 4: pp 51-62, 1998.

Tew, J.G. D. Qin, J. Wu, G.F. Burton, and A.K. Szakal: The Germinal Center Reaction: Influence of FDC Function in Normal, Aged, and Retrovirus Infected Hosts. In "The Biology of Germinal Centers in Lymphoid Tissue", Tsiagbe, V.K. and G.J. Thorbecke, Editors. Landes Austin Texas, Chapter 2: pp. 105-129, 1998.

Kapasi, A.F., D. Qin, W.G. Kerr, M.H. Kosco-Vilbois, L.D. Shultz, J.G. Tew and A.K. Szakal: Follicular dendritic cells (FDC) precursors in primary lymphoid tissues. J. Immunol. 160:1078-1084, 1998.

Qin, D., J. Wu, M.C. Carroll, G.F. Burton, A. K. Szakal and J.G. Tew: Evidence for an Important Interaction between a Complement Derived CD21 Ligand on Follicular Dendritic Cells and CD21 on B cells in the Initiation of IgG Responses. J. Immunol. 161:4549-4554, 1998.

Qin, D., J. Wu, G.F. Burton, A.K. Szakal and J.G. Tew: FDC mediated maintenance of Primary Lymphocyte Cultures for Long-Term Analysis of a Functional in vitro Immune System. J. Immunol. Methods. 226:19-27 1999.

Califano, J.V., R.E. Schifferle, J.C. Gunsolley, H.A. Schenkein and J.G. Tew: Antibody reactive with Porphoryomonas gingivalis serotypes K1-K6 in adult and generalized early onset periodontitis. J. Periodontal. 70:730-735, 1999.

Schenkein, H.A., J.C. Gunsolley, A.M. Best, M.T. Harrison, C.L. Hahn, J. Wu, and J.G.Tew: Human anti-phosphorylcholine antibody levels are elevated in persons with periodontal disease. Infect. Immun. 67:4814-1818, 1999.

Schwarz,Y.X., M. Yang, D. Qin, J. Wu, W.D. Jarvis, S. Grant, G.F. Burton, A.K. Szakal and John G. Tew: Follicular dendritic cells protect malignant B cells from apoptosis induced by anti-Fas and anti-neoplastic agents. J. Immunol. 163:6442-6447 1999.

Ishihara, Y., J.B. Zhang, S.M. Quinn, H.A. Schenkein, S.E. Barbour, and J.G. Tew: Regulation of IgG2 Production by Prostaglandin E2 and Platelet-Activating Factor. Infect. Immun. 68:1563-1568, 2000.

Tew, J.G. and A.K. Szakal: Macrophages, dendritic cells and follicular dendritic cells. Textbook of Rheumatology, Sixth Edition, Kelley, W.N., E.D. Harris, S. Ruddy and C.B. Sledge. W.B. Saunders Company, Philadelphia. (In Press) 2000.

Qin, D., J. Wu, K. A. Vora, J. V. Ravetch, A.K. Szakal, T. Manser and J.G. Tew: FcRIIB on follicular dendritic cells regulates the B cell recall response. J. Immunol. (In Press) 2000.

Schenkein, H.A, A.M. Best, C.N. Brooks, J.A. Burmeister, J.A. Arrowood,  M.C. Kontos, and J.G. Tew: Anti-Cardiolipin and Increased Serum Adhesion Molecule Levels in Patients with Aggressive Periodontitis. J. Periodontol. 78:459-466, 2007.

El Shikh, M. E., R.M. El Sayed, Y. Wu, A.K. Szakal, J.G. Tew:  Follicular Dendritic Cells Express TLR4 and Its Engagement Promotes Activation with Enhanced Accessory Activity. J. Immunol. 179:4444-4450, 2007.

Wu, Y., S. Sukumar, M. E. El Shikh, A.M. Best. A.K. Szakal, J.G. Tew: Immune Complex Bearing Follicular Dendritic Cells Deliver a Late Antigenic Signal that Promotes Somatic Hypermutation. J. Immunol. 180:281-90, 2008.

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