OHSU

Louis J. Picker

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 and cytomegalovirus, and are working on prophylactic and/or therapeutic vaccines against these pathogens. Finally, they are studying how memory T cells are reconstituted after HIV/SIV infection.

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.


Key Publications


Okoye A, Meier-Schellersheim M, Brenchley JM, Hagen SI, Walker JM, Rohankhedkar M, Lum R, Edgar J, Planer SL, Legasse A, Sylwester AW, Piatak, Jr, M, Lifson JD, Maino VC, Sodora DL, Douek DC, Axthelm MK, Grossman Z, and Picker LJ.  Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection.  J. Exp. Med., 204:2171-2185, 2007.

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.  Nat. Med., 15:293-299, 2009.

Okoye A, Park H, Rohankhedkar M, Coyne-Johnson L, Lum R, Walker JM, Planer SL, Legasse AW, Sylwester AW, Piatak, Jr., M, Lifson JD, Sodora DL, Axthelm MK, Schmitz JE, and Picker LJ.  Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis.  J. Exp. Med., 206:1575-1588, 2009.

Hansen SG, Ford JC, Lewis MS, Venture 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. (*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.

Okoye A, Rohankhedkar M, Abana C, Pattenn, A, Reyes M, Pexton C, Lum R, Sylweste 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 JL.  Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines.  Nature Med. 18:1673-1681, 2012.