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Department of Biology and the University of California at San Diego Cancer Center University of California at San Diego, La Jolla, CA 92093; and Trudeau Institute, Saranac Lake, NY 12983
The generation of memory T cells is critically important for rapid
clearance and neutralization of pathogens encountered previously by the
immune system. We have studied the kinetics of response and Ag dose
requirements for proliferation and cytokine secretion of
CD4+ memory T cells to examine whether there are
qualitative changes which might lead to improved immunity. TCR Tg
CD4+ T cells were primed in vitro and transferred into T
cell-deficient hosts. After 6 or more weeks, the persisting T cells
were exclusively small resting cells with a memory phenotype:
CD44high CD62L+/- CD25-. Memory
CD4 T cells showed a similar pattern of response as naive cells to
peptide analogues with similar Ag dose requirements for IL-2 secretion.
However, memory cells (derived from both Th2 and Th1 effectors)
displayed faster kinetics of cytokine secretion, cell division, and
proliferation, enhanced proliferation in response to low doses of Ag or
peptide analogues, and production of IL-4, IL-5, and IFN-
. These
results suggest there is a much more efficient response of CD4 memory T
cells to Ag re-exposure and that the expanded functional capacity of
memory cells will promote a rapid development of effector functions,
providing more rapid and effective immunity.
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M. S. Zand, B. J. Briggs, A. Bose, and T. Vo Discrete Event Modeling of CD4+ Memory T Cell Generation J. Immunol., September 15, 2004; 173(6): 3763 - 3772. [Abstract] [Full Text] [PDF]
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F. Andris, S. Denanglaire, F. de Mattia, J. Urbain, and O. Leo Naive T Cells Are Resistant to Anergy Induction by Anti-CD3 Antibodies J. Immunol., September 1, 2004; 173(5): 3201 - 3208. [Abstract] [Full Text] [PDF]
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C. S. Chin, C. H.T. Miller, L. Graham, M. Parviz, S. Zacur, B. Patel, A. Duong, and H. D. Bear Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L-selectinlow tumor-sensitized lymphocytes Int. Immunol., September 1, 2004; 16(9): 1283 - 1294. [Abstract] [Full Text] [PDF]
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B. P. Pappu and P. A. Shrikant Alteration of Cell Surface Sialylation Regulates Antigen-Induced Naive CD8+ T Cell Responses J. Immunol., July 1, 2004; 173(1): 275 - 284. [Abstract] [Full Text] [PDF]
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D. K. Sojka, D. Bruniquel, R. H. Schwartz, and N. J. Singh IL-2 Secretion by CD4+ T Cells In Vivo Is Rapid, Transient, and Influenced by TCR-Specific Competition J. Immunol., May 15, 2004; 172(10): 6136 - 6143. [Abstract] [Full Text] [PDF]
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L. Haynes, S. M. Eaton, E. M. Burns, M. Rincon, and S. L. Swain Inflammatory Cytokines Overcome Age-Related Defects in CD4 T Cell Responses In Vivo J. Immunol., May 1, 2004; 172(9): 5194 - 5199. [Abstract] [Full Text] [PDF]
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L.-X. Wang, J. Kjaergaard, P. A. Cohen, S. Shu, and G. E. Plautz Memory T Cells Originate from Adoptively Transferred Effectors and Reconstituting Host Cells after Sequential Lymphodepletion and Adoptive Immunotherapy J. Immunol., March 15, 2004; 172(6): 3462 - 3468. [Abstract] [Full Text] [PDF]
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 M. A. Aronica, S. McCarthy, S. Swaidani, D. Mitchell, M. Goral, J. R. Sheller, and M. Boothby Recall Helper T Cell Response: T Helper 1 Cell-resistant Allergic Susceptibility without Biasing Uncommitted CD4 T Cells Am. J. Respir. Crit. Care Med., March 1, 2004; 169(5): 587 - 595. [Abstract] [Full Text] [PDF]
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S.-A. Younes, B. Yassine-Diab, A. R. Dumont, M.-R. Boulassel, Z. Grossman, J.-P. Routy, and R.-P. Sekaly HIV-1 Viremia Prevents the Establishment of Interleukin 2-producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity J. Exp. Med., December 15, 2003; 198(12): 1909 - 1922. [Abstract] [Full Text] [PDF]
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B. Bellier, V. Thomas-Vaslin, M.-F. Saron, and D. Klatzmann Turning immunological memory into amnesia by depletion of dividing T cells PNAS, December 9, 2003; 100(25): 15017 - 15022. [Abstract] [Full Text] [PDF]
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F. G. Lakkis and M. H. Sayegh Memory T Cells: A Hurdle to Immunologic Tolerance J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2402 - 2410. [Full Text] [PDF]
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M. Iwata, Y. Eshima, and H. Kagechika Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors Int. Immunol., August 1, 2003; 15(8): 1017 - 1025. [Abstract] [Full Text] [PDF]
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K. Kimachi, K. Sugie, and H. M. Grey Effector T cells have a lower ligand affinity threshold for activation than naive T cells Int. Immunol., July 1, 2003; 15(7): 885 - 892. [Abstract] [Full Text] [PDF]
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 R. Mortarini, A. Piris, A. Maurichi, A. Molla, I. Bersani, A. Bono, C. Bartoli, M. Santinami, C. Lombardo, F. Ravagnani, et al. Lack of Terminally Differentiated Tumor-specific CD8+ T Cells at Tumor Site in Spite of Antitumor Immunity to Self-Antigens in Human Metastatic Melanoma Cancer Res., May 15, 2003; 63(10): 2535 - 2545. [Abstract] [Full Text] [PDF]
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J. M. Blander, D. B. Sant'Angelo, D. Metz, S.-W. Kim, R. A. Flavell, K. Bottomly, and C. A. Janeway Jr. A Pool of Central Memory-Like CD4 T Cells Contains Effector Memory Precursors J. Immunol., March 15, 2003; 170(6): 2940 - 2948. [Abstract] [Full Text] [PDF]
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T. N. J. Bullock, D. W. Mullins, and V. H. Engelhard Antigen Density Presented By Dendritic Cells In Vivo Differentially Affects the Number and Avidity of Primary, Memory, and Recall CD8+ T Cells J. Immunol., February 15, 2003; 170(4): 1822 - 1829. [Abstract] [Full Text] [PDF]
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S. A. Fadel, D. A. Ozaki, and M. Sarzotti Enhanced Type 1 Immunity After Secondary Viral Challenge in Mice Primed as Neonates J. Immunol., September 15, 2002; 169(6): 3293 - 3300. [Abstract] [Full Text] [PDF]
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L.-X. Wang, B.-G. Chen, and G. E. Plautz Adoptive Immunotherapy of Advanced Tumors with CD62 L-Selectinlow Tumor-Sensitized T Lymphocytes Following Ex Vivo Hyperexpansion J. Immunol., September 15, 2002; 169(6): 3314 - 3320. [Abstract] [Full Text] [PDF]
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K. Klugewitz, F. Blumenthal-Barby, A. Schrage, P. A. Knolle, A. Hamann, and I. N. Crispe Immunomodulatory Effects of the Liver: Deletion of Activated CD4+ Effector Cells and Suppression of IFN-{gamma}-Producing Cells After Intravenous Protein Immunization J. Immunol., September 1, 2002; 169(5): 2407 - 2413. [Abstract] [Full Text] [PDF]
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S. Zwaveling, S. C. F. Mota, J. Nouta, M. Johnson, G. B. Lipford, R. Offringa, S. H. van der Burg, and C. J. M. Melief Established Human Papillomavirus Type 16-Expressing Tumors Are Effectively Eradicated Following Vaccination with Long Peptides J. Immunol., July 1, 2002; 169(1): 350 - 358. [Abstract] [Full Text] [PDF]
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J. A. M. Borghans and R. J. De Boer Memorizing innate instructions requires a sufficiently specific adaptive immune system Int. Immunol., May 1, 2002; 14(5): 525 - 532. [Abstract] [Full Text] [PDF]
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C. Arpin, G. Angelov, T. Walzer, M. Tomkowiak, and J. Marvel Hyperproliferative Response of a Monoclonal Memory CD8 T Cell Population Is Characterized by an Increased Frequency of Clonogenic Precursors J. Immunol., March 1, 2002; 168(5): 2147 - 2153. [Abstract] [Full Text] [PDF]
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J. Harbertson, E. Biederman, K. E. Bennett, R. M. Kondrack, and L. M. Bradley Withdrawal of Stimulation May Initiate the Transition of Effector to Memory CD4 Cells J. Immunol., February 1, 2002; 168(3): 1095 - 1102. [Abstract] [Full Text] [PDF]
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M. A. C. de Lafaille, S. Muriglan, M.-J. Sunshine, Y. Lei, N. Kutchukhidze, G. C. Furtado, A. K. Wensky, D. Olivares-Villagomez, and J. J. Lafaille Hyper Immunoglobulin E Response in Mice with Monoclonal Populations of B and T Lymphocytes"" J. Exp. Med., November 5, 2001; 194(9): 1349 - 1360. [Abstract] [Full Text] [PDF]
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O. F. Bathe, N. Dalyot-Herman, and T. R. Malek IL-2 During In Vitro Priming Promotes Subsequent Engraftment and Successful Adoptive Tumor Immunotherapy by Persistent Memory Phenotypic CD8+ T Cells J. Immunol., October 15, 2001; 167(8): 4511 - 4517. [Abstract] [Full Text] [PDF]
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H. Gudmundsdottir and L. A. Turka A Closer Look at Homeostatic Proliferation of CD4+ T Cells: Costimulatory Requirements and Role in Memory Formation J. Immunol., October 1, 2001; 167(7): 3699 - 3707. [Abstract] [Full Text] [PDF]
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O. Adolfsson, B. T. Huber, and S. N. Meydani Vitamin E-Enhanced IL-2 Production in Old Mice: Naive But Not Memory T Cells Show Increased Cell Division Cycling and IL-2-Producing Capacity J. Immunol., October 1, 2001; 167(7): 3809 - 3817. [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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S. Mirshahidi, C.-T. Huang, and S. Sadegh-Nasseri Anergy in Peripheral Memory Cd4+ T Cells Induced by Low Avidity Engagement of T Cell Receptor J. Exp. Med., September 17, 2001; 194(6): 719 - 732. [Abstract] [Full Text] [PDF]
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O. Bruna-Romero, G. Gonzalez-Aseguinolaza, J. C. R. Hafalla, M. Tsuji, and R. S. Nussenzweig Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen PNAS, September 5, 2001; (2001) 191380898. [Abstract] [Full Text] [PDF]
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 R. N. Germain The Art of the Probable: System Control in the Adaptive Immune System Science, July 13, 2001; 293(5528): 240 - 245. [Abstract] [Full Text]
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L.-M. Stott, R. N. Barker, and S. J. Urbaniak Identification of alloreactive T-cell epitopes on the Rhesus D protein Blood, December 15, 2000; 96(13): 4011 - 4019. [Abstract] [Full Text] [PDF]
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J. Strong, Q. Wang, and N. Killeen Impaired survival of T helper cells in the absence of CD4 PNAS, February 27, 2001; 98(5): 2566 - 2571. [Abstract] [Full Text] [PDF]
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T. J. Sullivan, J. J. Letterio, A. van Elsas, M. Mamura, J. van Amelsfort, S. Sharpe, B. Metzler, C. A. Chambers, and J. P. Allison Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation PNAS, February 27, 2001; 98(5): 2587 - 2592. [Abstract] [Full Text] [PDF]
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O. Bruna-Romero, G. Gonzalez-Aseguinolaza, J. C. R. Hafalla, M. Tsuji, and R. S. Nussenzweig Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen PNAS, September 25, 2001; 98(20): 11491 - 11496. [Abstract] [Full Text] [PDF]
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