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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1667-1677
REVIEW ARTICLE
Dressed to kill? A review of why antiviral CD8 T lymphocytes fail
to prevent progressive immunodeficiency in HIV-1 infection
Judy Lieberman,
Premlata Shankar,
N. Manjunath, and
Jan Andersson
From the Center for Blood Research and Department of
Pediatrics, Harvard Medical School, Boston, MA; and the Division of
Infectious Diseases, Center for Infectious Medicine, Karolinska
Institutet, Huddinge University Hospital, Stockholm, Sweden.
CD8 T cells play an important role in protection and control of
HIV-1 by direct cytolysis of infected cells and by suppression of viral
replication by secreted factors. However, although HIV-1-infected individuals have a high frequency of HIV-1-specific CD8 T cells, viral
reservoirs persist and progressive immunodeficiency generally ensues in
the absence of continuous potent antiviral drugs. Freshly isolated
HIV-specific CD8 T cells are often unable to lyse HIV-1-infected cells. Maturation into competent cytotoxic T lymphocytes may be blocked
during the initial encounter with antigen because of defects in antigen
presentation by interdigitating dendritic cells or HIV-infected
macrophages. The molecular basis for impaired function is
multifactorial, due to incomplete T-cell signaling and activation (in
part related to CD3 and CD28 down-modulation), reduced perforin expression, and inefficient trafficking of HIV-specific CD8 T cells to
lymphoid sites of infection. CD8 T-cell dysfunction can partially
be corrected in vitro with short-term exposure to interleukin 2, suggesting that impaired HIV-specific CD4 T helper function may play a
significant causal or exacerbating role. Functional defects are
qualitatively different and more severe with advanced disease, when
interferon  production also becomes compromised.
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Related Letter in Blood Online:
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Why antiviral CD8 T lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection
- Carlo Agostini, Gianpietro Semenzato, Judy Lieberman, Premlata Shankar, M. Swamy, and Jan Andersson
Blood 2002 99: 1876-1878.
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M. Schweneker, D. Favre, J. N. Martin, S. G. Deeks, and J. M. McCune
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180(10):
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[PDF]
|
|
|
|
|
|
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E. Connick, T. Mattila, J. M. Folkvord, R. Schlichtemeier, A. L. Meditz, M. G. Ray, M. D. McCarter, S. MaWhinney, A. Hage, C. White, et al.
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J. Immunol.,
June 1, 2007;
178(11):
6975 - 6983.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-Y. Zhang, Z. Zhang, X. Wang, J.-L. Fu, J. Yao, Y. Jiao, L. Chen, H. Zhang, J. Wei, L. Jin, et al.
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Blood,
June 1, 2007;
109(11):
4671 - 4678.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Biancotto, J.-C. Grivel, S. J. Iglehart, C. Vanpouille, A. Lisco, S. F. Sieg, R. Debernardo, K. Garate, B. Rodriguez, L. B. Margolis, et al.
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May 15, 2007;
109(10):
4272 - 4279.
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[Full Text]
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|
|
|
|
|
|
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April 15, 2007;
109(8):
3351 - 3359.
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|
|
|
|
|
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178(6):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Hryniewicz, A. Boasso, Y. Edghill-Smith, M. Vaccari, D. Fuchs, D. Venzon, J. Nacsa, M. R. Betts, W.-P. Tsai, J.-M. Heraud, et al.
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December 1, 2006;
108(12):
3834 - 3842.
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|
|
|
|
|
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M. Guadalupe, S. Sankaran, M. D. George, E. Reay, D. Verhoeven, B. L. Shacklett, J. Flamm, J. Wegelin, T. Prindiville, and S. Dandekar
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80(16):
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|
|
|
|
|
|
|
S. Schneider-Schaulies and U. Dittmer
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87(6):
1423 - 1438.
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|
|
|
|
|
|
|
J. M. Beck
The Immunocompromised Host: HIV Infection
Proceedings of the ATS,
December 1, 2005;
2(5):
423 - 427.
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[Full Text]
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|
|
|
|
|
|
|
N. E. Miller, J. R. Bonczyk, Y. Nakayama, and M. Suresh
Role of Thymic Output in Regulating CD8 T-Cell Homeostasis during Acute and Chronic Viral Infection
J. Virol.,
August 1, 2005;
79(15):
9419 - 9429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Peretz, G. Alter, M.-P. Boisvert, G. Hatzakis, C. M. Tsoukas, and N. F. Bernard
Human Immunodeficiency Virus (HIV)-Specific Gamma Interferon Secretion Directed against All Expressed HIV Genes: Relationship to Rate of CD4 Decline
J. Virol.,
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79(8):
4908 - 4917.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Eggena, B. Barugahare, N. Jones, M. Okello, S. Mutalya, C. Kityo, P. Mugyenyi, and H. Cao
Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation
J. Immunol.,
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174(7):
4407 - 4414.
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[Full Text]
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|
|
|
|
|
|
|
T. Dong, G. Stewart-Jones, N. Chen, P. Easterbrook, X. Xu, L. Papagno, V. Appay, M. Weekes, C. Conlon, C. Spina, et al.
HIV-specific Cytotoxic T Cells from Long-Term Survivors Select a Unique T Cell Receptor
J. Exp. Med.,
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200(12):
1547 - 1557.
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[Full Text]
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|
|
|
|
|
|
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A. F. Ochsenbein, S. R. Riddell, M. Brown, L. Corey, G. M. Baerlocher, P. M. Lansdorp, and P. D. Greenberg
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December 6, 2004;
200(11):
1407 - 1417.
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|
|
|
|
|
|
|
M. Dagarag, T. Evazyan, N. Rao, and R. B. Effros
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J. Immunol.,
November 15, 2004;
173(10):
6303 - 6311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ueno, H. Tomiyama, M. Fujiwara, S. Oka, and M. Takiguchi
Functionally Impaired HIV-Specific CD8 T Cells Show High Affinity TCR-Ligand Interactions
J. Immunol.,
November 1, 2004;
173(9):
5451 - 5457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Borkow and Z. Bentwich
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Clin. Microbiol. Rev.,
October 1, 2004;
17(4):
1012 - 1030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. Bonaparte and E. Barker
Killing of human immunodeficiency virus-infected primary T-cell blasts by autologous natural killer cells is dependent on the ability of the virus to alter the expression of major histocompatibility complex class I molecules
Blood,
October 1, 2004;
104(7):
2087 - 2094.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Kinter, M. Hennessey, A. Bell, S. Kern, Y. Lin, M. Daucher, M. Planta, M. McGlaughlin, R. Jackson, S. F. Ziegler, et al.
CD25+CD4+ Regulatory T Cells from the Peripheral Blood of Asymptomatic HIV-infected Individuals Regulate CD4+ and CD8+ HIV-specific T Cell Immune Responses In Vitro and Are Associated with Favorable Clinical Markers of Disease Status
J. Exp. Med.,
August 2, 2004;
200(3):
331 - 343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Lichterfeld, X. G. Yu, M. T. Waring, S. K. Mui, M. N. Johnston, D. Cohen, M. M. Addo, J. Zaunders, G. Alter, E. Pae, et al.
HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8+ T cells producing both interferon-{gamma} and tumor necrosis factor-{alpha}
Blood,
July 15, 2004;
104(2):
487 - 494.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Shacklett, C. A. Cox, M. F. Quigley, C. Kreis, N. H. Stollman, M. A. Jacobson, J. Andersson, J. K. Sandberg, and D. F. Nixon
Abundant Expression of Granzyme A, but Not Perforin, in Granules of CD8+ T Cells in GALT: Implications for Immune Control of HIV-1 Infection
J. Immunol.,
July 1, 2004;
173(1):
641 - 648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
K. K. A. Van Rompay, R. P. Singh, B. Pahar, D. L. Sodora, C. Wingfield, J. R. Lawson, M. L. Marthas, and N. Bischofberger
CD8+-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment
J. Virol.,
May 15, 2004;
78(10):
5324 - 5337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Gherardi, E. Perez-Jimenez, J. L. Najera, and M. Esteban
Induction of HIV Immunity in the Genital Tract After Intranasal Delivery of a MVA Vector: Enhanced Immunogenicity After DNA Prime-Modified Vaccinia Virus Ankara Boost Immunization Schedule
J. Immunol.,
May 15, 2004;
172(10):
6209 - 6220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Homann, D. B. McGavern, and M. B. A. Oldstone
Visualizing the Viral Burden: Phenotypic and Functional Alterations of T Cells and APCs during Persistent Infection
J. Immunol.,
May 15, 2004;
172(10):
6239 - 6250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Suresh, X. Gao, C. Fischer, N. E. Miller, and K. Tewari
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J. Virol.,
April 15, 2004;
78(8):
3906 - 3918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhou, R. Ou, L. Huang, G. E. Price, and D. Moskophidis
Differential Tissue-Specific Regulation of Antiviral CD8+ T-Cell Immune Responses during Chronic Viral Infection
J. Virol.,
April 1, 2004;
78(7):
3578 - 3600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kinloch-de Loes
Role of therapeutic vaccines in the control of HIV-1
J. Antimicrob. Chemother.,
April 1, 2004;
53(4):
562 - 566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Fumero, F. Garcia, and J. M. Gatell
Immunosuppressive drugs as an adjuvant to HIV treatment
J. Antimicrob. Chemother.,
March 1, 2004;
53(3):
415 - 417.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Brenchley, B. J. Hill, D. R. Ambrozak, D. A. Price, F. J. Guenaga, J. P. Casazza, J. Kuruppu, J. Yazdani, S. A. Migueles, M. Connors, et al.
T-Cell Subsets That Harbor Human Immunodeficiency Virus (HIV) In Vivo: Implications for HIV Pathogenesis
J. Virol.,
February 1, 2004;
78(3):
1160 - 1168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ranjbar, N. Ly, S. Thim, J.-M. Reynes, and A. E. Goldfeld
Mycobacterium tuberculosis Recall Antigens Suppress HIV-1 Replication in Anergic Donor Cells via CD8+ T Cell Expansion and Increased IL-10 Levels
J. Immunol.,
February 1, 2004;
172(3):
1953 - 1959.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. V. Jensen, Y. Castelruiz, and B. Aasted
Cytokine Profiles in Adult Mink Infected with Aleutian Mink Disease Parvovirus
J. Virol.,
July 1, 2003;
77(13):
7444 - 7451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Bahr, X. De La Tribonniere, E. Darcissac, F. Ajana, L. Bocket, D. Sissoko, Y. Yazdanpanah, J. Dewulf, C. Amiel, and Y. Mouton
Clinical and immunological effects of a 6 week immunotherapy cycle with murabutide in HIV-1 patients with unsuccessful long-term antiretroviral treatment
J. Antimicrob. Chemother.,
June 1, 2003;
51(6):
1377 - 1388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. O. Yang, P. T. N. Sarkis, A. Ali, J. D. Harlow, C. Brander, S. A. Kalams, and B. D. Walker
Determinants of HIV-1 Mutational Escape From Cytotoxic T Lymphocytes
J. Exp. Med.,
May 19, 2003;
197(10):
1365 - 1375.
[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]
|
|
|
|
|
|
|
M. Dagarag, H. Ng, R. Lubong, R. B. Effros, and O. O. Yang
Differential Impairment of Lytic and Cytokine Functions in Senescent Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes
J. Virol.,
March 1, 2003;
77(5):
3077 - 3083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Kohler, D. L. Tuttle, C. R. Coberley, J. W. Sleasman, and M. M. Goodenow
Human immunodeficiency virus type 1 (HIV-1) induces activation of multiple STATs in CD4+ cells of lymphocyte or monocyte/macrophage lineages
J. Leukoc. Biol.,
March 1, 2003;
73(3):
407 - 416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
C. G. Lange and M. M. Lederman
Immune reconstitution with antiretroviral therapies in chronic HIV-1 infection
J. Antimicrob. Chemother.,
January 1, 2003;
51(1):
1 - 4.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Bahr
Non-specific immunotherapy of HIV-1 infection: potential use of the synthetic immunodulator murabutide
J. Antimicrob. Chemother.,
January 1, 2003;
51(1):
5 - 8.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Zhang, P. Shankar, Z. Xu, B. Harnisch, G. Chen, C. Lange, S. J. Lee, H. Valdez, M. M. Lederman, and J. Lieberman
Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic
Blood,
January 1, 2003;
101(1):
226 - 235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Buseyne, D. Scott-Algara, F. Porrot, B. Corre, N. Bellal, M. Burgard, C. Rouzioux, S. Blanche, and Y. Riviere
Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8+ T Cells in Infected Children Correlate Positively with Plasma Viral Load
J. Virol.,
November 13, 2002;
76(24):
12414 - 12422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. U. Vogel, H. Horton, D. H. Fuller, D. K. Carter, K. Vielhuber, D. H. O'Connor, T. Shipley, J. Fuller, G. Sutter, V. Erfle, et al.
Differences Between T Cell Epitopes Recognized After Immunization and After Infection
J. Immunol.,
October 15, 2002;
169(8):
4511 - 4521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lieberman
Defying Death -- HIV Mutation to Evade Cytotoxic T Lymphocytes
N. Engl. J. Med.,
October 10, 2002;
347(15):
1203 - 1204.
[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. E. Keir, M. G. Rosenberg, J. K. Sandberg, K. A. Jordan, A. Wiznia, D. F. Nixon, C. A. Stoddart, and J. M. McCune
Generation of CD3+CD8low Thymocytes in the HIV Type 1-Infected Thymus
J. Immunol.,
September 1, 2002;
169(5):
2788 - 2796.
[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]
|
|
|
|
|
|
|
C. Agostini, G. Semenzato, J. Lieberman, P. Shankar, M. Swamy, and J. Andersson
Why antiviral CD8 T lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection
Blood,
March 1, 2002;
99(5):
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[Full Text]
[PDF]
|
|
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