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CUTTING EDGE |
Infectious Diseases Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Recent analyses of CD8 T cell responses to Listeria monocytogenes infection demonstrate that the duration of in vivo T cell proliferation is not determined by the amount or duration of Ag presentation. However, the extent to which T lymphocytes are capable of proliferating in the absence of Ag is unknown. Herein we demonstrate that CD8 T lymphocytes undergo up to eight rounds of proliferation in the absence of Ag following transient, 2.5-h in vitro antigenic stimulation. Ag-independent expansion of CD8 T cells is driven by IL-2 and is further augmented by IL-7 or IL-15. These experiments clearly demonstrate that CD8 T cells undergo prolonged proliferation following transient Ag exposure and support the notion that in vivo CD8 T cell expansion following infection can be uncoupled from Ag presentation.
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J. N. Radcliffe, J. S. Roddick, F. K. Stevenson, and S. M. Thirdborough Prolonged Antigen Expression following DNA Vaccination Impairs Effector CD8+ T Cell Function and Memory Development J. Immunol., December 15, 2007; 179(12): 8313 - 8321. [Abstract] [Full Text] [PDF]
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E. Diaz-Guerra, R. Vernal, M. J. del Prete, A. Silva, and J. A. Garcia-Sanz CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells J. Immunol., December 1, 2007; 179(11): 7352 - 7357. [Abstract] [Full Text] [PDF]
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H.-R. Kim, K.-A Hwang, and I. Kang Dual Roles of IL-15 in Maintaining IL-7R{alpha}lowCCR7 Memory CD8+ T Cells in Humans via Recovering the Phosphatidylinositol 3-Kinase/AKT Pathway J. Immunol., November 15, 2007; 179(10): 6734 - 6740. [Abstract] [Full Text] [PDF]
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 M. Heffner and D. T. Fearon Loss of T cell receptor-induced Bmi-1 in the KLRG1+ senescent CD8+ T lymphocyte PNAS, August 14, 2007; 104(33): 13414 - 13419. [Abstract] [Full Text] [PDF]
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V. P. Badovinac and J. T. Harty Manipulating the Rate of Memory CD8+ T Cell Generation after Acute Infection J. Immunol., July 1, 2007; 179(1): 53 - 63. [Abstract] [Full Text] [PDF]
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 K.-J. Puan, C. Jin, H. Wang, G. Sarikonda, A. M. Raker, H. K. Lee, M. I. Samuelson, E. Marker-Hermann, L. Pasa-Tolic, E. Nieves, et al. Preferential recognition of a microbial metabolite by human V{gamma}2V{delta}2 T cells Int. Immunol., May 1, 2007; 19(5): 657 - 673. [Abstract] [Full Text] [PDF]
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M. L. Ford, B. H. Koehn, M. E. Wagener, W. Jiang, S. Gangappa, T. C. Pearson, and C. P. Larsen Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation J. Exp. Med., February 19, 2007; 204(2): 299 - 309. [Abstract] [Full Text] [PDF]
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C. Chiu, A. G. Heaps, V. Cerundolo, A. J. McMichael, C. R. Bangham, and M. F. C. Callan Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo Blood, February 1, 2007; 109(3): 1086 - 1094. [Abstract] [Full Text] [PDF]
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J. S. Haring and J. T. Harty Aberrant Contraction of Antigen-Specific CD4 T Cells after Infection in the Absence of Gamma Interferon or Its Receptor Infect. Immun., November 1, 2006; 74(11): 6252 - 6263. [Abstract] [Full Text] [PDF]
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M. Prlic, G. Hernandez-Hoyos, and M. J. Bevan Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response J. Exp. Med., September 4, 2006; 203(9): 2135 - 2143. [Abstract] [Full Text] [PDF]
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R. A. Willis, J. W. Kappler, and P. C. Marrack CD8 T cell competition for dendritic cells in vivo is an early event in activation PNAS, August 8, 2006; 103(32): 12063 - 12068. [Abstract] [Full Text] [PDF]
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W. N. D'Souza and S. M. Hedrick Cutting Edge: Latecomer CD8 T Cells Are Imprinted with a Unique Differentiation Program J. Immunol., July 15, 2006; 177(2): 777 - 781. [Abstract] [Full Text] [PDF]
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J. S. Yi, B. C. Holbrook, R. D. Michalek, N. G. Laniewski, and J. M. Grayson Electron Transport Complex I Is Required for CD8+ T Cell Function J. Immunol., July 15, 2006; 177(2): 852 - 862. [Abstract] [Full Text] [PDF]
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V. P. Badovinac, K. A. N. Messingham, T. S. Griffith, and J. T. Harty TRAIL Deficiency Delays, but Does Not Prevent, Erosion in the Quality of "Helpless" Memory CD8 T Cells J. Immunol., July 15, 2006; 177(2): 999 - 1006. [Abstract] [Full Text] [PDF]
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 N. K. Polakos, J. C. Cornejo, D. A. Murray, K. O. Wright, J. J. Treanor, I. N. Crispe, D. J. Topham, and R. H. Pierce Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection Am. J. Pathol., April 1, 2006; 168(4): 1169 - 1178. [Abstract] [Full Text] [PDF]
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B. B. Porter and J. T. Harty The Onset of CD8+-T-Cell Contraction Is Influenced by the Peak of Listeria monocytogenes Infection and Antigen Display Infect. Immun., March 1, 2006; 74(3): 1528 - 1536. [Abstract] [Full Text] [PDF]
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K. E. Foulds and H. Shen Clonal Competition Inhibits the Proliferation and Differentiation of Adoptively Transferred TCR Transgenic CD4 T Cells in Response to Infection. J. Immunol., March 1, 2006; 176(5): 3037 - 3043. [Abstract] [Full Text] [PDF]
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L. O. Atherly, M. A. Brehm, R. M. Welsh, and L. J. Berg Tec Kinases Itk and Rlk Are Required for CD8+ T Cell Responses to Virus Infection Independent of Their Role in CD4+ T Cell Help J. Immunol., February 1, 2006; 176(3): 1571 - 1581. [Abstract] [Full Text] [PDF]
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 R. C. Grabert, L. P. Cousens, J. A. Smith, S. Olson, J. Gall, W. B. Young, P. A. Davol, and L. G. Lum Human T Cells Armed with Her2/neu Bispecific Antibodies Divide, Are Cytotoxic, and Secrete Cytokines with Repeated Stimulation Clin. Cancer Res., January 15, 2006; 12(2): 569 - 576. [Abstract] [Full Text] [PDF]
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T.-C. Yang, J. Millar, T. Groves, N. Grinshtein, R. Parsons, S. Takenaka, Y. Wan, and J. L. Bramson The CD8+ T Cell Population Elicited by Recombinant Adenovirus Displays a Novel Partially Exhausted Phenotype Associated with Prolonged Antigen Presentation That Nonetheless Provides Long-Term Immunity J. Immunol., January 1, 2006; 176(1): 200 - 210. [Abstract] [Full Text] [PDF]
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I. Messaoudi, J. Warner, D. Nikolich-Zugich, M. Fischer, and J. Nikolich-Zugich Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo J. Immunol., January 1, 2006; 176(1): 301 - 308. [Abstract] [Full Text] [PDF]
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R. Polley, S. L. Sanos, S. Prickett, A. Haque, and P. M. Kaye Chronic Leishmania donovani Infection Promotes Bystander CD8+-T-Cell Expansion and Heterologous Immunity Infect. Immun., December 1, 2005; 73(12): 7996 - 8001. [Abstract] [Full Text] [PDF]
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A. Ploss, I. Leiner, and E. G. Pamer Distinct Regulation of H2-M3-Restricted Memory T Cell Responses in Lymph Node and Spleen J. Immunol., November 1, 2005; 175(9): 5998 - 6005. [Abstract] [Full Text] [PDF]
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M. A. Brehm, K. A. Daniels, and R. M. Welsh Rapid Production of TNF-{alpha} following TCR Engagement of Naive CD8 T Cells J. Immunol., October 15, 2005; 175(8): 5043 - 5049. [Abstract] [Full Text] [PDF]
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J. M. Curtsinger, D. C. Lins, C. M. Johnson, and M. F. Mescher Signal 3 Tolerant CD8 T Cells Degranulate in Response to Antigen but Lack Granzyme B to Mediate Cytolysis J. Immunol., October 1, 2005; 175(7): 4392 - 4399. [Abstract] [Full Text] [PDF]
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D. Wodarz and A. R. Thomsen Effect of the CTL proliferation program on virus dynamics Int. Immunol., September 1, 2005; 17(9): 1269 - 1276. [Abstract] [Full Text] [PDF]
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D. R. Drake III, R. M. Ream, C. W. Lawrence, and T. J. Braciale Transient Loss of MHC Class I Tetramer Binding after CD8+ T Cell Activation Reflects Altered T Cell Effector Function J. Immunol., August 1, 2005; 175(3): 1507 - 1515. [Abstract] [Full Text] [PDF]
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F. Gesbert, J.-L. Moreau, and J. Theze IL-2 Responsiveness of CD4 and CD8 lymphocytes: further investigations with human IL-2R{beta} transgenic mice Int. Immunol., August 1, 2005; 17(8): 1093 - 1102. [Abstract] [Full Text] [PDF]
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J. S. Haring, G. A. Corbin, and J. T. Harty Dynamic Regulation of IFN-{gamma} Signaling in Antigen-Specific CD8+ T Cells Responding to Infection J. Immunol., June 1, 2005; 174(11): 6791 - 6802. [Abstract] [Full Text] [PDF]
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R. Obst, H.-M. van Santen, D. Mathis, and C. Benoist Antigen persistence is required throughout the expansion phase of a CD4+ T cell response J. Exp. Med., May 16, 2005; 201(10): 1555 - 1565. [Abstract] [Full Text] [PDF]
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S. G. Kitchen, J. K. Whitmire, N. R. Jones, Z. Galic, C. M. R. Kitchen, R. Ahmed, and J. A. Zack The CD4 molecule on CD8+ T lymphocytes directly enhances the immune response to viral and cellular antigens PNAS, March 8, 2005; 102(10): 3794 - 3799. [Abstract] [Full Text] [PDF]
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A. Lang and J. Nikolich-Zugich Development and Migration of Protective CD8+ T Cells into the Nervous System following Ocular Herpes Simplex Virus-1 Infection J. Immunol., March 1, 2005; 174(5): 2919 - 2925. [Abstract] [Full Text] [PDF]
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M. A. Williams and M. J. Bevan Shortening the Infectious Period Does Not Alter Expansion of CD8 T Cells but Diminishes Their Capacity to Differentiate into Memory Cells J. Immunol., December 1, 2004; 173(11): 6694 - 6702. [Abstract] [Full Text] [PDF]
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A. Srinivasan, J. Foley, R. Ravindran, and S. J. McSorley Low-Dose Salmonella Infection Evades Activation of Flagellin-Specific CD4 T Cells J. Immunol., September 15, 2004; 173(6): 4091 - 4099. [Abstract] [Full Text] [PDF]
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R. M. Teague, R. M. Tempero, S. Thomas, K. Murali-Krishna, and B. H. Nelson Proliferation and Differentiation of CD8+ T Cells in the Absence of IL-2/15 Receptor {beta}-Chain Expression or STAT5 Activation J. Immunol., September 1, 2004; 173(5): 3131 - 3139. [Abstract] [Full Text] [PDF]
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S. Santra, D. H. Barouch, B. Korioth-Schmitz, C. I. Lord, G. R. Krivulka, F. Yu, M. H. Beddall, D. A. Gorgone, M. A. Lifton, A. Miura, et al. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses PNAS, July 27, 2004; 101(30): 11088 - 11093. [Abstract] [Full Text] [PDF]
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H. Starks, K. W. Bruhn, H. Shen, R. A. Barry, T. W. Dubensky, D. Brockstedt, D. J. Hinrichs, D. E. Higgins, J. F. Miller, M. Giedlin, et al. Listeria monocytogenes as a Vaccine Vector: Virulence Attenuation or Existing Antivector Immunity Does Not Diminish Therapeutic Efficacy J. Immunol., July 1, 2004; 173(1): 420 - 427. [Abstract] [Full Text] [PDF]
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P. Wong, M. Lara-Tejero, A. Ploss, I. Leiner, and E. G. Pamer Rapid Development of T Cell Memory J. Immunol., June 15, 2004; 172(12): 7239 - 7245. [Abstract] [Full Text] [PDF]
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 E. J. Wherry and R. Ahmed Memory CD8 T-Cell Differentiation during Viral Infection J. Virol., June 1, 2004; 78(11): 5535 - 5545. [Full Text] [PDF]
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 J. Skitzki, R. A. Craig, R. Okuyama, R. N. Knibbs, K. McDonagh, A. E. Chang, and L. M. Stoolman Donor Cell Cycling, Trafficking, and Accumulation during Adoptive Immunotherapy for Murine Lung Metastases Cancer Res., March 15, 2004; 64(6): 2183 - 2191. [Abstract] [Full Text] [PDF]
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R. C. Alaniz, S. Sandall, E. K. Thomas, and C. B. Wilson Increased Dendritic Cell Numbers Impair Protective Immunity to Intracellular Bacteria Despite Augmenting Antigen-Specific CD8+ T Lymphocyte Responses J. Immunol., March 15, 2004; 172(6): 3725 - 3735. [Abstract] [Full Text] [PDF]
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J. Chang, J.-H. Cho, S.-W. Lee, S.-Y. Choi, S.-J. Ha, and Y.-C. Sung IL-12 Priming during In Vitro Antigenic Stimulation Changes Properties of CD8 T Cells and Increases Generation of Effector and Memory Cells J. Immunol., March 1, 2004; 172(5): 2818 - 2826. [Abstract] [Full Text] [PDF]
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P. Wong and E. G. Pamer Disparate In Vitro and In Vivo Requirements for IL-2 During Antigen-Independent CD8 T Cell Expansion J. Immunol., February 15, 2004; 172(4): 2171 - 2176. [Abstract] [Full Text] [PDF]
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E. M. Bertram, W. Dawicki, B. Sedgmen, J. L. Bramson, D. H. Lynch, and T. H. Watts A Switch in Costimulation from CD28 to 4-1BB during Primary versus Secondary CD8 T Cell Response to Influenza In Vivo J. Immunol., January 15, 2004; 172(2): 981 - 988. [Abstract] [Full Text] [PDF]
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W. L. Redmond, J. Hernandez, and L. A. Sherman Deletion of Naive CD8 T Cells Requires Persistent Antigen and Is Not Programmed by an Initial Signal from the Tolerogenic APC J. Immunol., December 15, 2003; 171(12): 6349 - 6354. [Abstract] [Full Text] [PDF]
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K. Benlhassan-Chahour, C. Penit, V. Dioszeghy, F. Vasseur, G. Janvier, Y. Riviere, N. Dereuddre-Bosquet, D. Dormont, R. Le Grand, and B. Vaslin Kinetics of Lymphocyte Proliferation during Primary Immune Response in Macaques Infected with Pathogenic Simian Immunodeficiency Virus SIVmac251: Preliminary Report of the Effect of Early Antiviral Therapy J. Virol., December 1, 2003; 77(23): 12479 - 12493. [Abstract] [Full Text] [PDF]
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W. N. D'Souza and L. Lefrancois IL-2 Is Not Required for the Initiation of CD8 T Cell Cycling but Sustains Expansion J. Immunol., December 1, 2003; 171(11): 5727 - 5735. [Abstract] [Full Text] [PDF]
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J. M. Curtsinger, C. M. Johnson, and M. F. Mescher CD8 T Cell Clonal Expansion and Development of Effector Function Require Prolonged Exposure to Antigen, Costimulation, and Signal 3 Cytokine J. Immunol., November 15, 2003; 171(10): 5165 - 5171. [Abstract] [Full Text] [PDF]
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L. Lefrancois, A. Marzo, and K. Williams Sustained Response Initiation Is Required for T Cell Clonal Expansion But Not for Effector or Memory Development In Vivo J. Immunol., September 15, 2003; 171(6): 2832 - 2839. [Abstract] [Full Text] [PDF]
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 J. K. Damas, T. Waehre, A. Yndestad, K. Otterdal, A. Hognestad, N. O. Solum, L. Gullestad, S. S. Froland, and P. Aukrust Interleukin-7-Mediated Inflammation in Unstable Angina: Possible Role of Chemokines and Platelets Circulation, June 3, 2003; 107(21): 2670 - 2676. [Abstract] [Full Text] [PDF]
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V. P. Badovinac, K. A. Nordyke Messingham, S. E. Hamilton, and J. T. Harty Regulation of CD8+ T Cells Undergoing Primary and Secondary Responses to Infection in the Same Host J. Immunol., May 15, 2003; 170(10): 4933 - 4942. [Abstract] [Full Text] [PDF]
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N. Auphan-Anezin, G. Verdeil, and A.-M. Schmitt-Verhulst Distinct Thresholds for CD8 T Cell Activation Lead to Functional Heterogeneity: CD8 T Cell Priming Can Occur Independently of Cell Division J. Immunol., March 1, 2003; 170(5): 2442 - 2448. [Abstract] [Full Text] [PDF]
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G. C. Pien, K. B. Nguyen, L. Malmgaard, A. R. Satoskar, and C. A. Biron A Unique Mechanism for Innate Cytokine Promotion of T Cell Responses to Viral Infections J. Immunol., November 15, 2002; 169(10): 5827 - 5837. [Abstract] [Full Text] [PDF]
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J. M. Grayson, L. E. Harrington, J. G. Lanier, E. J. Wherry, and R. Ahmed Differential Sensitivity of Naive and Memory CD8+ T Cells to Apoptosis in Vivo J. Immunol., October 1, 2002; 169(7): 3760 - 3770. [Abstract] [Full Text] [PDF]
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A. G. Schrum and L. A. Turka The Proliferative Capacity of Individual Naive CD4+T Cells Is Amplified by Prolonged T Cell Antigen Receptor Triggering J. Exp. Med., September 16, 2002; 196(6): 793 - 803. [Abstract] [Full Text] [PDF]
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S.-K. Kim, M. A. Brehm, R. M. Welsh, and L. K. Selin Dynamics of Memory T Cell Proliferation Under Conditions of Heterologous Immunity and Bystander Stimulation J. Immunol., July 1, 2002; 169(1): 90 - 98. [Abstract] [Full Text] [PDF]
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E. M. Bertram, P. Lau, and T. H. Watts Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection J. Immunol., April 15, 2002; 168(8): 3777 - 3785. [Abstract] [Full Text] [PDF]
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K. E. Foulds, L. A. Zenewicz, D. J. Shedlock, J. Jiang, A. E. Troy, and H. Shen Cutting Edge: CD4 and CD8 T Cells Are Intrinsically Different in Their Proliferative Responses J. Immunol., February 15, 2002; 168(4): 1528 - 1532. [Abstract] [Full Text] [PDF]
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W. T. Lee, G. Pasos, L. Cecchini, and J. N. Mittler Continued Antigen Stimulation Is Not Required During CD4+ T Cell Clonal Expansion J. Immunol., February 15, 2002; 168(4): 1682 - 1689. [Abstract] [Full Text] [PDF]
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K. Takumi, J. Garssen, and A. Havelaar A quantitative model for neutrophil response and delayed-type hypersensitivity reaction in rats orally inoculated with various doses of Salmonella Enteritidis Int. Immunol., February 1, 2002; 14(2): 111 - 119. [Abstract] [Full Text] [PDF]
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W. Asavaroengchai, Y. Kotera, and J. J. Mule Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery PNAS, January 22, 2002; 99(2): 931 - 936. [Abstract] [Full Text] [PDF]
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