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Trudeau Institute, Saranac Lake, NY 12983
The goal of adoptive immunotherapy is to target a high number of
persisting effector cells to the site of a virus infection or tumor. In
this study, we compared the protective value of hemagglutinin
peptide-specific CD8 T cells generated from the clone-4 TCR-transgenic
mice, defined by different stages of their differentiation, against
lethal pulmonary influenza infection. We show that the adoptive
transfer of high numbers of Ag-specific unprimed, naive CD8 T cells
failed to clear the pulmonary virus titer and to promote host survival.
The same numbers of in vitro generated primary Ag-specific Tc1 effector
cells, producing high amounts of IFN-
, or resting Tc1 memory cells,
generated from these effectors, were protective. Highly activated
CD62Llow Tc1 effectors accumulated in the lung with rapid
kinetics and most efficiently reduced the pulmonary viral titer early
during infection. The resting CD62Lhigh naive and memory
populations first increased in cell numbers in the draining lymph
nodes. Subsequently, memory cells accumulated more rapidly and to a
greater extent in the lung lavage as compared with naive cells. Thus,
effector cells are most effective against a localized virus infection,
which correlates with their ability to rapidly distribute at the
infected tissue site. The finding that similar numbers of naive
Ag-specific CD8 T cells are not protective supports the view that
qualitative differences between the two resting populations, the naive
and the memory population, may play a major role in their protective
value against disease.
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P. M. Gray, S. Arimilli, E. M. Palmer, G. D. Parks, and M. A. Alexander-Miller Altered Function in CD8+ T Cells following Paramyxovirus Infection of the Respiratory Tract J. Virol., March 15, 2005; 79(6): 3339 - 3349. [Abstract] [Full Text] [PDF]
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N. Meidenbauer, J. Marienhagen, M. Laumer, S. Vogl, J. Heymann, R. Andreesen, and A. Mackensen Survival and Tumor Localization of Adoptively Transferred Melan-A-Specific T Cells in Melanoma Patients J. Immunol., February 15, 2003; 170(4): 2161 - 2169. [Abstract] [Full Text] [PDF]
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E. J. Wherry, M. J. McElhaugh, and L. C. Eisenlohr Generation of CD8+ T Cell Memory in Response to Low, High, and Excessive Levels of Epitope J. Immunol., May 1, 2002; 168(9): 4455 - 4461. [Abstract] [Full Text] [PDF]
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K. Fukada, Y. Sobao, H. Tomiyama, S. Oka, and M. Takiguchi Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells J. Immunol., March 1, 2002; 168(5): 2225 - 2232. [Abstract] [Full Text] [PDF]
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S.-i. Fujii, K. Shimizu, T. Shimizu, and M. T. Lotze Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ Blood, October 1, 2001; 98(7): 2143 - 2151. [Abstract] [Full Text] [PDF]
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B. K. Helmich and R. W. Dutton The Role of Adoptively Transferred CD8 T Cells and Host Cells in the Control of the Growth of the EG7 Thymoma: Factors That Determine the Relative Effectiveness and Homing Properties of Tc1 and Tc2 Effectors J. Immunol., June 1, 2001; 166(11): 6500 - 6508. [Abstract] [Full Text] [PDF]
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 D. R. Marshall, S. J. Turner, G. T. Belz, S. Wingo, S. Andreansky, M. Y. Sangster, J. M. Riberdy, T. Liu, M. Tan, and P. C. Doherty Measuring the diaspora for virus-specific CD8+ T cells PNAS, May 3, 2001; (2001) 101132698. [Abstract] [Full Text]
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M. Ahmadzadeh, S. F. Hussain, and D. L. Farber Heterogeneity of the Memory CD4 T Cell Response: Persisting Effectors and Resting Memory T Cells J. Immunol., January 15, 2001; 166(2): 926 - 935. [Abstract] [Full Text] [PDF]
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D. R. Marshall, S. J. Turner, G. T. Belz, S. Wingo, S. Andreansky, M. Y. Sangster, J. M. Riberdy, T. Liu, M. Tan, and P. C. Doherty Measuring the diaspora for virus-specific CD8+ T cells PNAS, May 22, 2001; 98(11): 6313 - 6318. [Abstract] [Full Text] [PDF]
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