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
1217 E. Marshall St., 320 Medical Sciences Building
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:

At the present time we have several projects being actively studied in the laboratory. In the first project we are trying to understand how the antibody response is maintained and regulated for years after immunization or recovery from infection. We find that antigen is trapped in the lymphoid tissues of the body by special cells called follicular dendritic cells (FDCs). These cells release some of this antigen on the surface of membrane bound vesicles in the form of immune complexes. These immune complex coated bodies (iccosomes) are extremely immunogenic, and we believe iccosome bound antigen helps induce the antibody response. In addition, the FDCs retain much of the antigen on their dendritic processes. Data from our laboratory support the concept that antigen persisting in association with FDCs functions in an antibody feedback system to maintain and regulate serum antibody levels including antibodies causing allergic reactions. Typically serum antibody levels are maintained for many months or years before a "booster" immunization is required. We believe that in the maintenance phase of the immune response FDCs continue to stimulate antibody production by releasing iccosomes from time to time and thus play a critical role in maintaining the level of antibody in the blood including antibodies that cause allergy. FDC function may allow us to better control infectious diseases and reduce allergy. In a related project we find that FDCs protect productive B cells from death caused by a process called apoptosis. This is very helpful when the host is mounting a productive immune response. Unfortunately, we also find that FDC can protect malignant B cells from apoptosis stimulated by chemotherapeutic drugs. Thus FDC can provide a sanctuary where certain cancer cells can be protected from chemotherapy. We are now trying to find ways to block FDC mediated protection and help make chemotherapy more efficacious.

In another project we are trying to understand how the immune response may contribute to the pathogenesis of periodontal disease. We have found that in addition to specific antigens, most periodontal organisms contain polyclonal activators and that many of these activators are potent mitogens. We think these polyclonal activators may enter the periodontal tissues, nonspecifically stimulate the immune system, and set up the chronic inflammation associated with periodontal disease. This hypothesis is currently being tested using a variety of in vitro and in vivo experimental systems. We also find that some patients that develop severe periodontal disease early in life have a tendency to make more dendritic cells and that these cells may also contribute to chronic inflammation. We are currently in the process of studying the function of dendritic cells in periodontal disease.
 

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.

Recent Publications (1994-2000):

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.

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