Phyllis-Jean Linton (Kaplan), Ph.D.
Immune function in the aged with an emphasis on dendritic cell/macrophage, and T cell alterations; relationship between autophagy and inflammation in infection and the ischemic heart.
Cornell University, Ithaca, NY / B.Sc. 1977 / Biology
Syracuse University, Syracuse, NY / M.Sc. 1981 / Immunology
Syracuse University, Syracuse, NY / Ph.D. 1984 / Immunology
Scripps Clinic and Research Foundation, CA / Postdoc. 1987 / Immunology
Positions and Employment
1984-1987 Postdoctoral Fellow, Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA.
1987-1991 Senior Research Associate, Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA.
1991-1994 Assistant Member, Department of Immunology, The Scripps Research Institute, La Jolla, CA.
1994-2005 Guest Visiting Scientist, Department of Immunology, The Scripps Research Institute, La Jolla, CA.
1994-1997 Assistant Professor, Sidney Kimmel Cancer Center, San Diego, CA.
1997-2009 Associate Professor, Sidney Kimmel Cancer Center, San Diego, CA.
2009-present Adjunct Professor, San Diego State University, San Diego, CA.
2009-present Professor, San Diego State University Research Foundation, San Diego, CA.
Memberships, Honors, and Awards
1983-1984 Syracuse University Fellowship.
1993, 1998 Invited Participant, NIH Workshop on T and B Cell Memory.
1999 NIAID Focus Group.
1999, 2001-2003 GRM/NIH Study Section, adhoc member.
2000, 2005 Grant Reviewer, Pilot/Feasibility Grants, Geriatrics Center's Claude Pepper Older Americans Independence Center.
2000-2003 IMB/NIH Study Section, adhoc member.
2002, 2007, 2009 AFAR National Scientific Advisory Council.
2002, 2004 Invited Participant, NIH Workshop on Immunobiology and Aging.
2003 Wellcome Trust Training Fellowship, ad hoc reviewer.
2003-2004 SEP/NIH Study Section, adhoc member (shared instrumentation - flow cytometers).
2003 Aging Research and Education Center - Pilot Grant Reviewer.
2003-2006 CMAD/NIH Study Section, member.
2004 SEP/NIH Study Section, adhoc reviewer (Nathan Shock Aging Centers).
2004 Concept review panel for NIA Office of Biological Resources and Resource Development (genetic monitoring of NIA rodent colonies).
2006 Research in Aging, grant reviewer.
2007, 2008 SEP/NIH Study Section, reviewer (P01: Effect of Damage Autophagy and Aging).
2007 Invited Speaker, 33rd Annual La Jolla Immunology Conference.
2008 NIH SEP NCCAM ZAT1 SM Study Section, adhoc reviewer.
2008 Symposia co-chair, FASEB AAI meeting.
2008 Invited Speaker/Participant, United States-Japan Cooperative Medical Science Program-sponsored Immunosenescence Workshop.
2008 Invited Speaker, Beeson Scholars Scientific Meeting.
2009 NIH SEP RFA "Partnering Awards to Support Collaborative Research on the Biology of Aging."
2009 NIH CMAD/NIH Study Section, adhoc reviewer.
2010-2012 NIH Study Section, Biomedical Research on the International Space Station, reviewer.
2010 NIH SEP ZRG BDA-C Study Section, adhoc reviewer.
2012-2016 ASH/NIH Study Section, member.
2012 Invited Speaker, AHA Symposia
Selected Peer-Reviewed Publications
Kaplan, P.-J. and Garvey, J.S. (1986) Mycoplasma neurolyticum membranes: a T-independent antigen in the rat. Immunological Investigations, 15:35.
Klinman, N.R. and Linton, P.-J. (1986) The specificity and affinity of B cell triggering. In: Proceedings of 10th International Convocation on Immunology. Longman Group, Essex, England. Vol. 1, p. 125.
Klinman, N.R. and Linton, P.-J. (1988) The clonotype repertoire of B cell subpopulations. Advances Immunol, 42:1.
Linton, P.-J., Gilmore, G.L. and Klinman, N.R. (1988) The secondary B cell lineage. In: B Cell Development. UCLA Symposia on Molecular and Cellular Biology, New Series. O. Witte, M. Howard and N. Klinman, eds. Alan R. Liss, Inc., NY, v. 85, p. 75.
Pinkert, C.A., Manz, J., Linton, P.-J., Klinman, N.R. and Storb, U. (1989) Elevated PC responsive B cells and anti-PC antibody production in transgenic mice harboring anti-PC immunoglobulin genes. Vet. Immunol. Immunopathol., 23:321.
Linton, P.-J., and Klinman, N.R. (1989) Self non-self discrimination by precursors of memory B cells. In: Progress in Immunology, Vol. 7, Springer-Verlag, Heidelberg, p. 424.
Riley, S.C., Froscher, B.G., Linton, P.-J., Zharhary, D., Marcu, K. and Klinman, N.R. (1989) Altered VH gene utilization in responses to phosphorylcholine of aged mice. J. Immunol., 143:3798.
Linton, P.-J., Decker, D. and Klinman, N.R. (1989) Primary antibody responses and secondary B cells are generated from separate precursor cell populations. Cell, 59:1049.
Klinman, N.R., Riley, S.C., Zharhary, D., Froscher, B.G., Powers, G.D. and Linton, P.-J. (1990) Alterations in B cells and antibodies of aged mice. In: Biomedical Advances in Aging '88. Proceedings of the 8th International Washington Spring Symposium. Plenum Press, p. 349.
Klinman, N.R. and Linton, P.-J. (1990) The generation of B cell memory: A working hypothesis. In: Current Topics in Microbiology and Immunology. J. Sprent and D. Gray, eds., Springer-Verlag, Heidelberg, p. 19.
Linton, P.-J., Rudie, A. and Klinman, N.R. (1991) Tolerance susceptibility of newly generating memory B cells. J. Immunol., 146:4099.
Lo, D., Sandren, E., Linton, P.-J., Behringer, R., Rexroad, C., Pursel, V., Palmiter, R.D. and Brinster, R.L. (1991) Expression of mouse IgA by transgenic mice, pigs and sheep. Eur. J. Immunol., 21:1001.
Linton, P.-J. (1992) B lymphocyte repertoire. In: Encyclopedia of Immunology. I.M. Roitt and P.J. Delves, eds. W.B. Saunders Co., London, pp. 239.
Linton, P.-J. and Klinman, N.R. (1992) The generation of memory B cells, In: Seminars in Immunology, edited by D. Gray. W.B. Saunders Co., London, England, 4:3.
Linton, P.-J., Lo, D., Lai, L., Thorbecke, G.J. and Klinman, N.R. (1992) Among naive precursor cell subpopulations only progenitors of memory B cells originate germinal centers. Eur. J. Immunol., 22:1293.
Tsiagbe, V.K., Linton, P.-J. and Thorbecke, G.J. (1992) The path of memory B cell development. Immunol. Rev., 126:113.
Linton, P.-J. Klinman, N.R. (1992) The use of the splenic focus assay to study B cell tolerance. Immunomethods, 1:1.
Linton, P.-J. (1993) Tolerance induction of newly generated memory B cells from aged mice. AGING: Immunology & Infectious Disease, 4:35.
Linton, P.-J. and Klinman, N.R. (1993) Functionality of B cell subsets in aged mice. AGING: Immunology & Infectious Disease, 4:135.
Stillman, C.A., Linton, P.-J., Koutz, P.J., Decker, D.J., Klinman, N.R. and Gingeras, T.R. (1994) Specific immunoglobulin cDNA clones produced from hybridoma cell lines and murine spleen fragment cultures by 3SR amplification. PCR Methods and Application, 3:320.
Klinman, N.R., Linton, P.-J. and Decker, D. (1995) Aging-associated immune dysfunction and strategies to delay its onset. In: Delaying the Onset of Late-Life Dysfunction. R.N. Butler and J. Brody, eds., Spring Publishing, NY, p. 53.
Decker, D.J., Linton, P.-J., Jacobs, S.N., Biery, M., Gingeras, T.R. and Klinman, N.R. (1995) Defining subsets of naive and memory B cells based on their ability to somatically mutate in vitro. Immunity, 2:195.
Linton, P.-J., Haynes, L., Klinman, N.R., and Swain, S. (1996). Antigen-independent changes in naive CD4 T cells with aging. J. Exp. Med., 184:1891.
Haynes, L., Linton, P.-J., and Swain, S.L. (1997) Age-related changes in CD4 T cells of T cell receptor transgenic mice. Mechanisms of Ageing and Development, 93:95.
Linton, P.-J., Haynes, L., Tsui, L., Zhang, X., and Swain, S. (1997) From naive to effector - alterations with aging. Immunol. Rev., 160:9.
Linton, P.-J. (1998) B lymphocyte repertoire, In: Encyclopedia of Immunology. I.M. Roitt and P.J. Delves, eds. Academic Press, London, pp. 359.
Haynes, L., Linton, P.-J., Eaton, S.M., Tonkonogy, S.L., and Swain, S.L. (1999) IL-2, but not other common chain (c)-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice. J. Exp. Med., 190:1013.
Bradley, L.M., Harbertson, J., Freschi, G.C., Kondrack, R., and Linton, P.-J. (2000) Regulation of the development and function of memory CD4 subsets. Immunol Res., 21(2-3):149-58.
Linton, P.-J., Harbertson, J., and Bradley, L.M. (2000) A critical role for B cells in the development of memory CD4 cells. J. Immunol., 165:5558-5565.
Linton, P.-J. and Thoman, M.L. (2001) T cell senescence. Front. Biosciences 6:248-261.
Li, S.P., Shi, W., Brunmark, A., Jackson, M., Cai, Z. and Linton, P.-J. (2002) Early antigen-specific response by naive CD8 T cells is not altered with aging. J. Immunol., 168:6120-6127.
Bradley, L.M., Harbertson, J.H., Biederman, E., Zhang, Y., Bradley, S.M., and Linton, P.-J. (2002) Availability of APC can determine the extent of CD4 effector expansion and priming for secretion of Th2 cytokines in vivo. Eur. J. Immunol., 32:2338-2346.
Linton, P.-J., Bautista, B., Biederman, E., Bradley, E.S., Harbertson, J., Kondrack, R.M., Padrick, R.C., and Bradley, L.M. (2003) Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo. J. Exp. Med., 197:875-883.
Effros, R., Cai, Z., and Linton, P.-J. (2003) CD8 T cells and aging. Crit. Rev. Immunol., 23(1&2):61-80.
Zhang, L., Tang, Y., Akbulut, H., Zelterman, D., Linton, P.-J., and Deisseroth, A.B. (2003) Injection of Ad vector encoding secretable form of TAA/CD40L fusion protein induces T cell dependent immune response for over a year against tumor cells. Proc. Natl. Acad. Sci., 100:15101-15106.
Linton, P.-J. and Dorshkind, K. (2004) Age-Related Changes in Lymphocyte Development and Function. Nature Immunol., 5(2):133-139.
Tang, Y., Zhang, L., Yuan, J., Akbulut, H., Maynard, J., Linton, P.-J., Deisseroth, A.B. (2004) Multi-Step Process Through Which Adenoviral Vector Vaccine Overcomes Anergy to Tumor Associated Antigens. Blood, 104(9):2704-13.
Linton, P.-J., Li, S.P., Zhang, Y., Bautista, B., Huynh, Q., and Trinh, T. (2005) Intrinsic vs. Environmental Influences on T Cell Responses in Aging. Immunol. Rev., 205:207-219.
Linton, P.-J., Lustgarten, J., Thoman, M. (2006). T cell Function in the Aged: Lessons Learned from Animal Models. Clin. Appl. Immunol. Rev., 6:73-97
Tang, Y., Akbulut, H., Maynard, J., Petersen, L., Fang, X., Zhang, W.W., Xia, X., Koziol, J., Linton, P. J., and Deisseroth, A. (2006) Vector prime/protein boost vaccine that overcomes defects acquired during aging and cancer. J. Immunol., 177:5697-5707.
Kovacs, E.J., Palmer, J., Fortin, C.F., Fulop Jr., T., Goldstein, D.R., and Linton, P.-J. (2009) Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol, 30:319-324.
Tang, Y, Thoman, M., Linton, P.J., and Deisseroth, A. (2009) Use of CD40L immunoconjugates to overcome the defective immune response to vaccines for infections and cancer in the aged. Cancer Immunol. Immunotherapy, 58:1949-57.
Gottlieb, R.A., Mentzer Jr., R.M., and Linton, P.-J. (2011) Impaired mitophagy at the heart of injury. Autophagy. 7:1573-1574.
Gottlieb, R.A. and Linton, P.-J., (2012) Indigestible mitochondria cause heartburn. Cell Res. 22:1518-20.
Gurney, M., Muralidhar, G., and Linton, P.-J. (2012) Autophagy and the immune response, In “Autophagy in Health and Disease”, (RA Gottlieb, Ed.), Academic Press/Elsevier.
Gurney, M.A., Huang, C., Ramil, J.M., Ravindran, N., Andres A.M., Linton, P.-J., and Gottlieb, R.A. (in press) Measuring cardiac autophaghic flux in vitro and in vivo In “Methods in Molecular Biology” ( A. Alvero and G. Mor, Eds.,) Humana Press.
P01 HL112725 (Gottlieb) • 06/01/13 - 05/30/17 • NIH/NHLBI
“Mitochondrial Quality Control in Cardioprotection: Overcoming Comorbidities”
Project 2 (Linton) "Age-related changes in autophagy and effects on inflammation and the heart"
The major goal of this project is to test the hypothesis that autophagy and inflammation in the cardiac ischemia/reperfusion (I/R) model are interdependent and modulation of autophagy will affect levels of inflammation and hence the severity of cardiac injury post I/R.
R01 AG026727 (Linton) • 02/15/07 - 01/31/12 • NIH/NIA
"Dendritic cells in the aged"
The major goals of this project are to define age-associated changes in DC function, to determine the effect of these changes on T cell responses, and to define ways to overcome DC deficiencies.
R21 AG031511 (Linton) • 08/15/08 - 07/31/10 • NIH/NIA
"Regulatory T cells in the influenza response of the aged"
The goals of this project are to elucidate the mechanism for the increased presence of Tregs in the aged and to determine the relative contribution by Tregs to the overall decline with aging in the immune response to influenza virus infection.
R01 AG019249 (Linton) • 05/01/01 - 04/30/07 • NIH/NIA
"Antigen responses by CD4 T cells of the aged"
The Specific Aims of the proposal were: 1) examine the IL-2 deficiency in effector cell generation in vivo and in vitro; 2) examine antigen specific CD4 T cell memory responses; 3) determine if alterations in the longevity/turnover/cell death (antigen independent) of naive T cells in the periphery of the aged contribute to the deficiency in IL-2 production.