| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
Dissecting the mechanisms of T cell-mediated immunity requires the
identification of functional characteristics and surface markers that
distinguish between activated and memory T lymphocytes. In this study,
we compared the rates of cytokine production by virus-specific primary
and memory CD8+ T cells directly ex vivo. Ag-specific
IFN-
and TNF-
production by both primary and long-term memory T
cells was observed in 
60 min after peptide stimulation. Although the
on-rate kinetics of cytokine production were nearly identical,
activated T cells produced more IFN-, but less TNF-, than memory
T cells. Ag-specific cytokine synthesis was not a constitutive process
and terminated immediately following disruption of contact with
peptide-coated cells, demonstrating that continuous antigenic
stimulation was required by both T cell populations to maintain
steady-state cytokine production. Upon re-exposure to Ag, activated T
cells resumed cytokine production whereas only a subpopulation of
memory T cells reinitiated cytokine synthesis. Analysis of cytokine
profiles and levels of CD8, LFA-1, and CTLA-4 together revealed a
pattern of expression that clearly distinguished in vivo-activated T
cells from memory T cells. Surprisingly, CTLA-4 expression was highest
at the early stages of the immune response but fell to background
levels soon after viral clearance. This study is the first to show that
memory T cells have the same Ag-specific on/off regulation of cytokine
production as activated T cells and demonstrates that memory T cells
can be clearly discriminated from activated T cells directly ex vivo by
their cytokine profiles and the differential expression of three
well-characterized T cell markers.
This article has been cited by other articles:
|
|
 |
|
  W. Zhou, J. Longmate, S. F. Lacey, J. M. Palmer, G. Gallez-Hawkins, L. Thao, R. Spielberger, R. Nakamura, S. J. Forman, J. A. Zaia, et al. Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients Blood, June 18, 2009; 113(25): 6465 - 6476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mooij, S. S. Balla-Jhagjhoorsingh, N. Beenhakker, P. van Haaften, I. Baak, I. G. Nieuwenhuis, S. Heidari, H. Wolf, M.-J. Frachette, K. Bieler, et al. Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens J. Virol., June 1, 2009; 83(11): 5881 - 5889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Henry, D. A. Ornelles, L. M. Mitchell, K. L. Brzoza-Lewis, and E. M. Hiltbold IL-12 Produced by Dendritic Cells Augments CD8+ T Cell Activation through the Production of the Chemokines CCL1 and CCL17 J. Immunol., December 15, 2008; 181(12): 8576 - 8584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Marques, M. C-J. Cheeran, J. M. Palmquist, S. Hu, S. L. Urban, and J. R. Lokensgard Prolonged Microglial Cell Activation and Lymphocyte Infiltration following Experimental Herpes Encephalitis J. Immunol., November 1, 2008; 181(9): 6417 - 6426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. U. Bielinska, A. A. Chepurnov, J. J. Landers, K. W. Janczak, T. S. Chepurnova, G. D. Luker, and J. R. Baker Jr. A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine Clin. Vaccine Immunol., February 1, 2008; 15(2): 348 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Kemball, E. Szomolanyi-Tsuda, and A. E. Lukacher Allogeneic Differences in the Dependence on CD4+ T-Cell Help for Virus-Specific CD8+ T-Cell Differentiation J. Virol., December 15, 2007; 81(24): 13743 - 13753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kannanganat, B. G. Kapogiannis, C. Ibegbu, L. Chennareddi, P. Goepfert, H. L. Robinson, J. Lennox, and R. R. Amara Human Immunodeficiency Virus Type 1 Controllers but Not Noncontrollers Maintain CD4 T Cells Coexpressing Three Cytokines J. Virol., November 1, 2007; 81(21): 12071 - 12076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kannanganat, C. Ibegbu, L. Chennareddi, H. L. Robinson, and R. R. Amara Multiple-Cytokine-Producing Antiviral CD4 T Cells Are Functionally Superior to Single-Cytokine-Producing Cells J. Virol., August 15, 2007; 81(16): 8468 - 8476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Whitmire, B. Eam, N. Benning, and J. L. Whitton Direct Interferon-{gamma} Signaling Dramatically Enhances CD4+ and CD8+ T Cell Memory J. Immunol., July 15, 2007; 179(2): 1190 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Rosenberg CTLA4, T cell function, and long term immunity: an interview with Dr. Mark K. Slifka J. Leukoc. Biol., May 1, 2007; 81(5): 1176 - 1178. [Full Text] [PDF]
|
|
|
|
|
|
H.-P. Raue and M. K. Slifka Pivotal Advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection J. Leukoc. Biol., May 1, 2007; 81(5): 1165 - 1175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cornberg, B. S. Sheridan, F. M. Saccoccio, M. A. Brehm, and L. K. Selin Protection against Vaccinia Virus Challenge by CD8 Memory T Cells Resolved by Molecular Mimicry J. Virol., January 15, 2007; 81(2): 934 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Ndejembi, J. R. Teijaro, D. S. Patke, A. W. Bingaman, M. R. Chandok, A. Azimzadeh, S. G. Nadler, and D. L. Farber Control of Memory CD4 T Cell Recall by the CD28/B7 Costimulatory Pathway J. Immunol., December 1, 2006; 177(11): 7698 - 7706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Grayson, A. E. Weant, B. C. Holbrook, and D. Hildeman Role of Bim in Regulating CD8+ T-Cell Responses during Chronic Viral Infection. J. Virol., September 1, 2006; 80(17): 8627 - 8638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lauterbach, E. I. Zuniga, P. Truong, M. B.A. Oldstone, and D. B. McGavern Adoptive immunotherapy induces CNS dendritic cell recruitment and antigen presentation during clearance of a persistent viral infection J. Exp. Med., August 7, 2006; 203(8): 1963 - 1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. C. Tscharke, W.-P. Woo, I. G. Sakala, J. Sidney, A. Sette, D. J. Moss, J. R. Bennink, G. Karupiah, and J. W. Yewdell Poxvirus CD8+ T-Cell Determinants and Cross-Reactivity in BALB/c Mice. J. Virol., July 1, 2006; 80(13): 6318 - 6323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kan-Mitchell, M. Bajcz, K. L. Schaubert, D. A. Price, J. M. Brenchley, T. E. Asher, D. C. Douek, H. L. Ng, O. O. Yang, C. R. Rinaldo Jr., et al. Degeneracy and Repertoire of the Human HIV-1 Gag p1777-85 CTL Response. J. Immunol., June 1, 2006; 176(11): 6690 - 6701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Whitmire, N. Benning, and J. L. Whitton Precursor Frequency, Nonlinear Proliferation, and Functional Maturation of Virus-Specific CD4+ T Cells. J. Immunol., March 1, 2006; 176(5): 3028 - 3036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. Homann, W. Dummer, T. Wolfe, E. Rodrigo, A. N. Theofilopoulos, M. B. A. Oldstone, and M. G. von Herrath Lack of Intrinsic CTLA-4 Expression Has Minimal Effect on Regulation of Antiviral T-Cell Immunity J. Virol., January 1, 2006; 80(1): 270 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Parameswaran, R. Suresh, V. Bal, S. Rath, and A. George Lack of ICAM-1 on APCs during T Cell Priming Leads to Poor Generation of Central Memory Cells J. Immunol., August 15, 2005; 175(4): 2201 - 2211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Freeman and H. K. Ziegler Simultaneous Th1-Type Cytokine Expression Is a Signature of Peritoneal CD4+ Lymphocytes Responding to Infection with Listeria monocytogenes J. Immunol., July 1, 2005; 175(1): 394 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Kemball, E. D. H. Lee, V. Vezys, T. C. Pearson, C. P. Larsen, and A. E. Lukacher Late Priming and Variability of Epitope-Specific CD8+ T Cell Responses during a Persistent Virus Infection J. Immunol., June 15, 2005; 174(12): 7950 - 7960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Patke and D. L. Farber Modulation of Memory CD4 T Cell Function and Survival Potential by Altering the Strength of the Recall Stimulus J. Immunol., May 1, 2005; 174(9): 5433 - 5443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Andreansky, J. Stambas, P. G. Thomas, W. Xie, R. J. Webby, and P. C. Doherty Consequences of Immunodominant Epitope Deletion for Minor Influenza Virus-Specific CD8+-T-Cell Responses J. Virol., April 1, 2005; 79(7): 4329 - 4339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beadling and M. K. Slifka Differential regulation of virus-specific T-cell effector functions following activation by peptide or innate cytokines Blood, February 1, 2005; 105(3): 1179 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Corbin and J. T. Harty T Cells Undergo Rapid ON/OFF but Not ON/OFF/ON Cycling of Cytokine Production in Response to Antigen J. Immunol., January 15, 2005; 174(2): 718 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-P. Raue, J. D. Brien, E. Hammarlund, and M. K. Slifka Activation of Virus-Specific CD8+ T Cells by Lipopolysaccharide-Induced IL-12 and IL-18 J. Immunol., December 1, 2004; 173(11): 6873 - 6881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ramakrishna, S. A. Stohlman, R. A. Atkinson, D. R. Hinton, and C. C. Bergmann Differential Regulation of Primary and Secondary CD8+ T Cells in the Central Nervous System J. Immunol., November 15, 2004; 173(10): 6265 - 6273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bartholdy, A. Stryhn, J. P. Christensen, and A. R. Thomsen Single-Epitope DNA Vaccination Prevents Exhaustion and Facilitates a Broad Antiviral CD8+ T Cell Response during Chronic Viral Infection J. Immunol., November 15, 2004; 173(10): 6284 - 6293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Kirby, M. Sundquist, and M. J. Wick In Vivo Compartmentalization of Functionally Distinct, Rapidly Responsive Antigen-Specific T-Cell Populations in DNA-Immunized or Salmonella enterica Serovar Typhimurium-Infected Mice Infect. Immun., November 1, 2004; 72(11): 6390 - 6400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Laniewski and J. M. Grayson Antioxidant Treatment Reduces Expansion and Contraction of Antigen-Specific CD8+ T Cells during Primary but Not Secondary Viral Infection J. Virol., October 15, 2004; 78(20): 11246 - 11257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Boissonnas, C. Combadiere, E. Lavergne, M. Maho, C. Blanc, P. Debre, and B. Combadiere Antigen Distribution Drives Programmed Antitumor CD8 Cell Migration and Determines Its Efficiency J. Immunol., July 1, 2004; 173(1): 222 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liu, J. L. Whitton, and M. K. Slifka The Rapidity with Which Virus-Specific CD8+ T Cells Initiate IFN-{gamma} Synthesis Increases Markedly over the Course of Infection and Correlates with Immunodominance J. Immunol., July 1, 2004; 173(1): 456 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. N. Kristensen, A. N. Madsen, A. R. Thomsen, and J. P. Christensen Cytokine production by virus-specific CD8+ T cells varies with activation state and localization, but not with TCR avidity J. Gen. Virol., June 1, 2004; 85(6): 1703 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Gold, M. W. Munks, M. Wagner, C. W. McMahon, A. Kelly, D. G. Kavanagh, M. K. Slifka, U. H. Koszinowski, D. H. Raulet, and A. B. Hill Murine Cytomegalovirus Interference with Antigen Presentation Has Little Effect on the Size or the Effector Memory Phenotype of the CD8 T Cell Response J. Immunol., June 1, 2004; 172(11): 6944 - 6953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Juedes, E. Rodrigo, L. Togher, L. H. Glimcher, and M. G. von Herrath T-bet Controls Autoaggressive CD8 Lymphocyte Responses in Type 1 Diabetes J. Exp. Med., April 19, 2004; 199(8): 1153 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Khanolkar, M. J. Fuller, and A. J. Zajac CD4 T Cell-Dependent CD8 T Cell Maturation J. Immunol., March 1, 2004; 172(5): 2834 - 2844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Bodman-Smith, V. M. Corrigall, D. M. Kemeny, and G. S. Panayi BiP, a putative autoantigen in rheumatoid arthritis, stimulates IL-10-producing CD8-positive T cells from normal individuals Rheumatology, May 1, 2003; 42(5): 637 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Wherry, J. N. Blattman, K. Murali-Krishna, R. van der Most, and R. Ahmed Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment J. Virol., April 15, 2003; 77(8): 4911 - 4927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zipris, J.-L. Hillebrands, R. M. Welsh, J. Rozing, J. X. Xie, J. P. Mordes, D. L. Greiner, and A. A. Rossini Infections That Induce Autoimmune Diabetes in BBDR Rats Modulate CD4+CD25+ T Cell Populations J. Immunol., April 1, 2003; 170(7): 3592 - 3602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Bergmann, B. Parra, D. R. Hinton, R. Chandran, M. Morrison, and S. A. Stohlman Perforin-Mediated Effector Function Within the Central Nervous System Requires IFN-{gamma}-Mediated MHC Up-Regulation J. Immunol., March 15, 2003; 170(6): 3204 - 3213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Rubinstein, A. N. Kadima, M. L. Salem, C. L. Nguyen, W. E. Gillanders, M. I. Nishimura, and D. J. Cole Transfer of TCR Genes into Mature T Cells Is Accompanied by the Maintenance of Parental T Cell Avidity J. Immunol., February 1, 2003; 170(3): 1209 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Slifka, J. N. Blattman, D. J. D. Sourdive, F. Liu, D. L. Huffman, T. Wolfe, A. Hughes, M. B. A. Oldstone, R. Ahmed, and M. G. von Herrath Preferential Escape of Subdominant CD8+ T Cells During Negative Selection Results in an Altered Antiviral T Cell Hierarchy J. Immunol., February 1, 2003; 170(3): 1231 - 1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Fuller and A. J. Zajac Ablation of CD8 and CD4 T Cell Responses by High Viral Loads J. Immunol., January 1, 2003; 170(1): 477 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, N. Silvestri, J. L. Whitton, and D. E. Hassett Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell Responses to DNA Vaccines J. Virol., October 25, 2002; 76(23): 11911 - 11919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Kristensen, J. P. Christensen, and A. R. Thomsen High numbers of IL-2-producing CD8+ T cells during viral infection: correlation with stable memory development J. Gen. Virol., September 1, 2002; 83(9): 2123 - 2133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sedegah, G. T. Brice, W. O. Rogers, D. L. Doolan, Y. Charoenvit, T. R. Jones, V. F. Majam, A. Belmonte, M. Lu, M. Belmonte, et al. Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8+-T-Cell Populations Infect. Immun., July 1, 2002; 70(7): 3493 - 3499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Haglund, I. Leiner, K. Kerksiek, L. Buonocore, E. Pamer, and J. K. Rose Robust Recall and Long-Term Memory T-Cell Responses Induced by Prime-Boost Regimens with Heterologous Live Viral Vectors Expressing Human Immunodeficiency Virus Type 1 Gag and Env Proteins J. Virol., June 27, 2002; 76(15): 7506 - 7517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liu, S. Andreansky, G. Diaz, T. Hogg, and P. C. Doherty Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of {gamma}-Herpesvirus-Infected CD4-Deficient Mice J. Immunol., April 1, 2002; 168(7): 3477 - 3483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Harrington, R. v. d. Most, J. L. Whitton, and R. Ahmed Recombinant Vaccinia Virus-Induced T-Cell Immunity: Quantitation of the Response to the Virus Vector and the Foreign Epitope J. Virol., March 7, 2002; 76(7): 3329 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pewe and S. Perlman Cutting Edge: CD8 T Cell-Mediated Demyelination Is IFN-{gamma} Dependent in Mice Infected with a Neurotropic Coronavirus J. Immunol., February 15, 2002; 168(4): 1547 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Tvinnereim, S. E. Hamilton, and J. T. Harty CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by Recombinant Listeria monocytogenes during Secondary Infection Infect. Immun., January 1, 2002; 70(1): 153 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. J. Turner, R. Cross, W. Xie, and P. C. Doherty Concurrent Naive and Memory CD8+ T Cell Responses to an Influenza A Virus J. Immunol., September 1, 2001; 167(5): 2753 - 2758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rodriguez, M. K. Slifka, S. Harkins, and J. L. Whitton Two Overlapping Subdominant Epitopes Identified by DNA Immunization Induce Protective CD8+ T-Cell Populations with Differing Cytolytic Activities J. Virol., August 15, 2001; 75(16): 7399 - 7409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Christen, T. Wolfe, U. Mohrle, A. C. Hughes, E. Rodrigo, E. A. Green, R. A. Flavell, and M. G. von Herrath A Dual Role for TNF-{{alpha}} in Type 1 Diabetes: Islet-Specific Expression Abrogates the Ongoing Autoimmune Process When Induced Late but Not Early During Pathogenesis J. Immunol., June 15, 2001; 166(12): 7023 - 7032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Belz, W. Xie, and P. C. Doherty Diversity of Epitope and Cytokine Profiles for Primary and Secondary Influenza A Virus-Specific CD8+ T Cell Responses J. Immunol., April 1, 2001; 166(7): 4627 - 4633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. P. Badovinac, A. R. Tvinnereim, and J. T. Harty Regulation of Antigen-Specific CD8+ T Cell Homeostasis by Perforin and Interferon-gamma Science, November 17, 2000; 290(5495): 1354 - 1357. [Abstract] [Full Text]
|
|
|
|
|
|
V. P. Badovinac, G. A. Corbin, and J. T. Harty Cutting Edge: OFF Cycling of TNF Production by Antigen-Specific CD8+ T Cells Is Antigen Independent J. Immunol., November 15, 2000; 165(10): 5387 - 5391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Shankar, M. Russo, B. Harnisch, M. Patterson, P. Skolnik, and J. Lieberman Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection Blood, November 1, 2000; 96(9): 3094 - 3101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Hassett, M. K. Slifka, J. Zhang, and J. L. Whitton Direct Ex Vivo Kinetic and Phenotypic Analyses of CD8+ T-Cell Responses Induced by DNA Immunization J. Virol., September 15, 2000; 74(18): 8286 - 8291. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
