Some T cells are the immune system's memory chips. Before the immune system can mount an effective attack on a disease-causing microorganism, they must form a subset of "memory" T cells specific for that organism. These "memory" T cells orchestrate immune elimination of the invader and remain in the blood and tissues so that the system can mount another counterattack should the foreign agent invade again. Memory T cell activity is also the key to explaining how vaccines work. Vaccines expose the immune system to weakened or noninfectious forms of pathogens, thus activating T cell memory and tricking the system into generating these critical disease-fighting cells. Researchers in Louis Picker's laboratory focus their studies on memory T cell biology in human and nonhuman primates. They investigate the physiology of T cell memory and effector responses, including mechanisms that control "selection" of the memory repertoire, the functional specialization of the memory population, and the elements involved in T cell homeostasis and regeneration. At the same time, these scientists are seeking to determine the basis of effective immunity to certain chronic human pathogens, particularly HIV/SIV, Mycobacterium tuberculosis, and cytomegalovirus, and are working on prophylactic and/or therapeutic vaccines against these pathogens. Picker and his colleagues have developed special expertise in the quantification and functional characterization of antigen-specific memory T cells. They exploit these technologies in the examination of human subjects and rhesus macaque models of chronic viral infection.

Biography

Louis Picker graduated from UCLA with a B.S. in bacteriology in 1978 and took his M.D. degree at the University of California at San Francisco in 1982. After residency training in pathology at Beth Israel Hospital, Boston, and postdoctoral training in immunology at Stanford University Medical Center, he was appointed assistant professor and then associate professor of pathology at the University of Texas Southwestern Medical Center at Dallas. In 1999 he came to OHSU and ONPRC as professor of pathology/molecular microbiology and immunology in the OHSU School of Medicine and head of the Division of Pathobiology and Immunology.

Selected publications

• Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, Legasse AW, Axthelm MK, Oswald K, Trubey CM, Piatak, Jr. M, Lifson JD, Nelson JA, Jarvis MA, and Picker LJ.  Effector-memory T cell responses are associated with protection of rhesus monkeys from mucosal SIV challenge. Nature Med. 15:293-299, 2009 [PMID: 19219024; PMCID: PMC2720091].
• Hansen SG, Powers C, Richards R, Ventura AB, Ford JC, Siess D, Axthelm MK, Nelson JA, Jarvis MA, Picker LJ*, and Früh K*. Evasion of CD8+ T cells is critical for super-infection by cytomegalovirus. Science 328:102-106, 2010 [PMID: 20360110; PMCID: PMC2883175]. (*co-corresponding authors).
• Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson^, T, Legasse AW, Axthelm MK, Nelson JA, Jarvis MA, Parks CL, Chiuchiolo MJ, Piatak, Jr. M, Lifson JD, and Picker^, LJ. Profound early control of highly pathogenic SIV by an effector-memory T cell vaccine. Nature 473:523-527, 2011 (doi:10.1038/nature10003).
• Okoye AA, Rohankhedkar M, Abana C, Pattenn A, Reyes M, Pexton C, Lum R, Sylwester A, Planer SL, Legasse A, Piatak, Jr. M, Lifson JD, Axthelm MK, and Picker LJ.  Naïve T cells are dispensable for CD4+ memory T cell homeostasis in progressive SIV infection. J. Exp. Med. 209:641-651, 2012.
• Fukazawa Y, Park H, Cameron MJ, Lefebvre F, Lum R, Coombes N, Mahyari E, Hagen S, Bae JY, Delos Reyes III M, Swanson T, Legasse AW, Sylwester A, Hansen SG, Smith AT, Stafova P, Shoemaker R, Li Y, Oswald K, Axthelm MK, McDermott A, Ferrari G, Montefiori DC, Edlefsen PT, Piatak, Jr. M, Lifson JD, Sékaly RP, and Picker LJ. Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. Nature Med. 18:1673-1681, 2012 (doi:10.1038/ nm.2934).
• Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, Gilbride RM, Lewis MS, Gilliam AN, Ventura AB, Malouli D, Xu G, Richards R, Whizin N, Reed JS, Hammond KB, Fischer M, Turner JM, Legasse AW, Axthelm MK, Edlefsen PT, Nelson JA, Lifson JD, Früh K, and Picker LJ. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science, 340(6135):1237874, 2013 (doi: 10.1126/science.1237874)
• Hansen SG, Piatak, Jr. M, Ventura AB, Hughes CM, Gilbride RM, Ford JC, Oswald K, Shoemaker R, Li Y, Lewis MS, Gilliam AN, Xu G, Whizin N, Planner SL, Turner JM, Legasse AW, Axthelm MK, Fukazawa Y, Park H, Edlefsen PT, Nelson JA, Früh K, Sacha JB, Estes JD, Lifson JD, and Picker LJ. Immune clearance of highly pathogenic SIV infection. Nature 502:100-104, 2013 (doi:10.1038/nature12519).
• Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, Hagen SI, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse AW, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch VM, Edlefsen PT, Piatak Jr. M, Lifson JD, and Picker LJ. B cell follicle sanctuary permits persistent productive SIV infection in elite controllers, Nature Med., 21:132-9, 2015. (doi:10.1038/nm.3781).
• Hansen SG, Wu HL, Burwitz BJ, Hughes CM, Hammond KB, Ventura AB, Reed JS, Gilbride RM, Ainslie E, Morrow DW, Ford JC, Selseth AN, Pathak R, Malouli D, Legasse AW, Axthelm MK, Nelson JA, Gillespie GM, Walters LC, Brackenridge S, Sharpe HR, López CA, Früh K, Korber B, McMichael AJ, Gnanakaran S, Sacha JB, and Picker LJ. Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex-E, Science, 351:714-720, 2016.  [10.1126/ science.aac9475]
• DeGottardi MQ, Okoye AA, Vaidya M, Talla A, Konfe AL, Reyes MD, Clock JA, Duell DM, Planner SS, Legassse AW, Sabnis A, Park BS, Axthelm MK, Estes, JD, Sekaly R-P, and Picker LJ. Effect of anti-IL-15 administration on T cell and NK cell homeostasis in rhesus macaques, J. Immunol, 197(4):1183-98, 2016. Pre-published online July 18, 2016, doi:10.4049/Jimmunol. 1600065.
• Hansen SG, Zak DE, Xu G, Ford JC, Marshall EE, Malouli D, Gilbride RM, Hughes CM, Ventura AB, Ainslie E, Randall KT, Selseth AN, Rundstrom P, Herlache L, Lewis MS, Park H, Planer SL, Turner JM, Fischer M, Armstrong C, Zweig RC, Sylwester AW, Legasse AW, Messerle M, Jarvis MA, Amon LM, Aderem A, Alter G, Laddy DJ, Stone M, Bonavia A, Evans TG, Messerle M, Jarvis MA, Früh K, Axthelm MK, Edlefsen PT and Picker LJ. Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine, Nature Med, 24:130-143, 2018; doi:10.1038/nm.4473 (2018).
• Okoye AA, Hansen SG, Vaidya M, Fukazawa Y, Park HM, Duell DM, Lum R, Hughes CM, Ventura AB, Ainslie E, Ford JC, Morrow D, Gilbride RM, Legasse AW, Hesselgesser J, Geleziunas, Li Y, Oswald K, Shoemaker R, Fast R, Bosche WJ, Borate BR, Edlefsen PT, Axthelm MK, Picker LJ*, and Lifson JD*. Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound, Nature Med, 2018 Aug 6. doi: 10.1038/s41591-018-0130-7. [Epub ahead of print] (*co-corresponding authors)