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CUTTING EDGE |
*
Naval Medical Research Institute, Bethesda, MD 20889;
Walter Reed Army Institute for Research, Rockville, MD 20850;
Henry M. Jackson Foundation for the Advancement of Military Medicine, U.S. Military HIV Research Program, Bethesda, MD 20889; and
§
Genetics Institute, Inc., Cambridge, MA 02140
We have assessed the functional effects of a panel of CTLA-4 mAbs on resting human CD4+ T cells. Our results demonstrate that some CTLA-4 mAbs can inhibit proliferative responses of resting CD4+ cells and cell cycle transition from G0 to G1. The inhibitory effects of CTLA-4 were evident within 4 h, at a time when cell surface CTLA-4 expression remained undetectable. Other CTLA-4 mAbs had no detectable inhibitory effects, indicating that binding of Ab to CTLA-4 alone is not sufficient to mediate down-regulation of T cell responses. Interestingly, while IL-2 production was shut off, inhibitory anti-CTLA-4 mAbs permitted induction and expression of the cell survival gene bcl-XL. Consistent with this observation, cells remained viable and apoptosis was not detected after CTLA-4 ligation.
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Y. Yi, M. McNerney, and S. K. Datta Regulatory Defects in Cbl and Mitogen-Activated Protein Kinase (Extracellular Signal-Related Kinase) Pathways Cause Persistent Hyperexpression of CD40 Ligand in Human Lupus T Cells J. Immunol., December 1, 2000; 165(11): 6627 - 6634. [Abstract] [Full Text] [PDF]
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T. Iida, H. Ohno, C. Nakaseko, M. Sakuma, M. Takeda-Ezaki, H. Arase, E. Kominami, T. Fujisawa, and T. Saito Regulation of Cell Surface Expression of CTLA-4 by Secretion of CTLA-4-Containing Lysosomes Upon Activation of CD4+ T Cells J. Immunol., November 1, 2000; 165(9): 5062 - 5068. [Abstract] [Full Text] [PDF]
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G. J. Freeman, A. J. Long, Y. Iwai, K. Bourque, T. Chernova, H. Nishimura, L. J. Fitz, N. Malenkovich, T. Okazaki, M. C. Byrne, et al. Engagement of the PD-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation J. Exp. Med., October 2, 2000; 192(7): 1027 - 1034. [Abstract] [Full Text] [PDF]
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B. M. Carreno, F. Bennett, T. A. Chau, V. Ling, D. Luxenberg, J. Jussif, M. L. Baroja, and J. Madrenas CTLA-4 (CD152) Can Inhibit T Cell Activation by Two Different Mechanisms Depending on Its Level of Cell Surface Expression J. Immunol., August 1, 2000; 165(3): 1352 - 1356. [Abstract] [Full Text] [PDF]
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M. D. Griffin, D. K. Hong, P. O. Holman, K.-M. Lee, M. J. Whitters, S. M. O'Herrin, F. Fallarino, M. Collins, D. M. Segal, T. F. Gajewski, et al. Blockade of T Cell Activation Using a Surface-Linked Single-Chain Antibody to CTLA-4 (CD152) J. Immunol., May 1, 2000; 164(9): 4433 - 4442. [Abstract] [Full Text] [PDF]
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M. L. Baroja, D. Luxenberg, T. Chau, V. Ling, C. A. Strathdee, B. M. Carreno, and J. Madrenas The Inhibitory Function of CTLA-4 Does Not Require Its Tyrosine Phosphorylation J. Immunol., January 1, 2000; 164(1): 49 - 55. [Abstract] [Full Text] [PDF]
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F. P. Heinzel and R. A. Maier Jr. Interleukin-4-Independent Acceleration of Cutaneous Leishmaniasis in Susceptible BALB/c Mice following Treatment with Anti-CTLA4 Antibody Infect. Immun., December 1, 1999; 67(12): 6454 - 6460. [Abstract] [Full Text] [PDF]
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C. Nakaseko, S. Miyatake, T. Iida, S. Hara, R. Abe, H. Ohno, Y. Saito, and T. Saito Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) Engagement Delivers an Inhibitory Signal through the Membrane-proximal Region in the Absence of the Tyrosine Motif in the Cytoplasmic Tail J. Exp. Med., September 20, 1999; 190(6): 765 - 774. [Abstract] [Full Text] [PDF]
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P. J. Perrin, C. H. June, J. H. Maldonado, R. B. Ratts, and M. K. Racke Blockade of CD28 During In Vitro Activation of Encephalitogenic T Cells or After Disease Onset Ameliorates Experimental Autoimmune Encephalomyelitis J. Immunol., August 1, 1999; 163(3): 1704 - 1710. [Abstract] [Full Text] [PDF]
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C. A. Chambers, M. S. Kuhns, and J. P. Allison Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4+ T cell responses PNAS, July 20, 1999; 96(15): 8603 - 8608. [Abstract] [Full Text] [PDF]
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J. L. Riley, K. Schlienger, P. J. Blair, B. Carreno, N. Craighead, D. Kim, R. G. Carroll, and C. H. June Modulation of Susceptibility to HIV-1 Infection by the Cytotoxic T Lymphocyte Antigen 4 Costimulatory Molecule J. Exp. Med., June 6, 1999; 191(11): 1987 - 1998. [Abstract] [Full Text] [PDF]
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R. Khattri, J. A. Auger, M. D. Griffin, A. H. Sharpe, and J. A. Bluestone Lymphoproliferative Disorder in CTLA-4 Knockout Mice Is Characterized by CD28-Regulated Activation of Th2 Responses J. Immunol., May 15, 1999; 162(10): 5784 - 5791. [Abstract] [Full Text] [PDF]
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M. C. Brunner, C. A. Chambers, F. K.-M. Chan, J. Hanke, A. Winoto, and J. P. Allison CTLA-4-Mediated Inhibition of Early Events of T Cell Proliferation J. Immunol., May 15, 1999; 162(10): 5813 - 5820. [Abstract] [Full Text] [PDF]
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D. Saverino, C. Tenca, D. Zarcone, A. Merlo, A. M. Megiovanni, M. T. Valle, F. Manca, C. E. Grossi, and E. Ciccone CTLA-4 (CD152) Inhibits the Specific Lysis Mediated by Human Cytolytic T Lymphocytes in a Clonally Distributed Fashion J. Immunol., January 15, 1999; 162(2): 651 - 658. [Abstract] [Full Text] [PDF]
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 C.A. CHAMBERS and J.P. ALLISON CTLA-4 -- The Costimulatory Molecule That Doesn't: Regulation of T-cell Responses by Inhibition Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 303 - 312. [Abstract] [PDF]
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M.-L. Alegre, H. Shiels, C. B. Thompson, and T. F. Gajewski Expression and Function of CTLA-4 in Th1 and Th2 Cells J. Immunol., October 1, 1998; 161(7): 3347 - 3356. [Abstract] [Full Text] [PDF]
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K. Schlienger, K. Uyemura, D. Jullien, P. A. Sieling, T. H. Rea, P. S. Linsley3, and R. L. Modlin B7-1, But Not CD28, Is Crucial for the Maintenance of the CD4+ T Cell Responses in Human Leprosy J. Immunol., September 1, 1998; 161(5): 2407 - 2413. [Abstract] [Full Text] [PDF]
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P. Scheipers and H. Reiser Fas-independent death of activated CD4+ T lymphocytes induced by CTLA-4 crosslinking PNAS, August 18, 1998; 95(17): 10083 - 10088. [Abstract] [Full Text] [PDF]
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J. H. Horspool, P. J. Perrin, J. B. Woodcock, J. H. Cox, C. L. King, C. H. June, D. M. Harlan, D. C. St. Louis, and K. P. Lee Nucleic Acid Vaccine-Induced Immune Responses Require CD28 Costimulation and Are Regulated by CTLA4 J. Immunol., March 15, 1998; 160(6): 2706 - 2714. [Abstract] [Full Text] [PDF]
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