Previous Article | Next Article 
Journal of Virology, February 2000, p. 1648-1657, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Cytokine Expression, Natural Killer Cell Activation, and
Phenotypic Changes in Lymphoid Cells from Rhesus Macaques during Acute
Infection with Pathogenic Simian Immunodeficiency Virus
Luis D.
Giavedoni,1,2,*
M.
Cristina
Velasquillo,1
Laura M.
Parodi,1
Gene B.
Hubbard,2,3 and
Vida L.
Hodara1
Department of Virology and
Immunology,1 Department of Laboratory
Animal Medicine,3 and Southwest Regional
Primate Research Center,2 Southwest Foundation
for Biomedical Research, San Antonio, Texas 78245
Received 5 August 1999/Accepted 10 November 1999
We studied the innate and adaptive immune system of rhesus macaques
infected with the virulent simian immunodeficiency virus isolate
SIVmac251 by evaluating natural killer (NK) cell activity, cytokine
levels in plasma, humoral and virological parameters, and changes in
the activation markers CD25 (interleukin 2R [IL-2R]
chain), CD69
(early activation marker), and CD154 (CD40 ligand) in lymphoid cells.
We found that infection with SIVmac251 induced the sequential
production of interferon-
/
(IFN-
/
), IL-18, and IL-12.
IFN-
, IL-4, and granulocyte-macrophage colony-stimulating factor
were undetected in plasma by the assays used. NK cell activity peaked
at 1 to 2 weeks postinfection and paralleled changes in viral loads.
Maximum expression of CD69 on CD3
CD16+
lymphocytes correlated with NK cytotoxicity during this period. CD25
expression, which is associated with proliferation, was static or
slightly down-regulated in CD4+ T cells from both
peripheral blood (PB) and lymph nodes (LN). CD69, which is normally
present in LN CD4+ T cells and absent in peripheral blood
leukocyte (PBL) CD4+ T cells, was down-regulated in LN
CD4+ T cells and up-regulated in PBL CD4+ T
cells immediately after infection. CD8+ T cells increased
CD69 but not CD25 expression, indicating the activation of this
cellular subset in PB and LN. Finally, CD154 was transiently
up-regulated in PBL CD4+ T cells but not in LN
CD4+ T cells. Levels of antibodies to SIV Gag and Env did
not correlate with the level of activation of CD154, a critical
costimulatory molecule for T-cell-dependent immunity. In summary, we
present the first documented evidence that the innate immune system of rhesus macaques recognizes SIV infection by sequential production of
proinflammatory cytokines and transient activation of NK cytotoxic activity. Additionally, pathogenic SIV induces drastic changes in the
level of activation markers on T cells from different anatomic compartments. These changes involve activation in the absence of
proliferation, indicating that activation-induced cell death may cause
some of the reported increase in lymphocyte turnover during SIV infection.
*
Corresponding author. Mailing address: Southwest
Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX
78245-0549. Phone: (210) 258-9603. Fax: (210) 670-3310. E-mail:
Lgiavedo{at}icarus.sfbr.org.
Journal of Virology, February 2000, p. 1648-1657, Vol. 74, No. 4
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Durudas, A., Milush, J. M., Chen, H.-L., Engram, J. C., Silvestri, G., Sodora, D. L.
(2009). Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys. J. Virol.
83: 12229-12240
[Abstract]
[Full Text]
-
Mselle, T. F., Howell, A. L., Ghosh, M., Wira, C. R., Sentman, C. L.
(2009). Human Uterine Natural Killer Cells but Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection by Secretion of CXCL12. J. Virol.
83: 11188-11195
[Abstract]
[Full Text]
-
Iannello, A., Samarani, S., Debbeche, O., Ahmad, R., Boulassel, M.-R., Tremblay, C., Toma, E., Routy, J.-P., Ahmad, A.
(2009). Potential Role of Interleukin-18 in the Immunopathogenesis of AIDS: Involvement in Fratricidal Killing of NK Cells. J. Virol.
83: 5999-6010
[Abstract]
[Full Text]
-
Malleret, B., Maneglier, B., Karlsson, I., Lebon, P., Nascimbeni, M., Perie, L., Brochard, P., Delache, B., Calvo, J., Andrieu, T., Spreux-Varoquaux, O., Hosmalin, A., Le Grand, R., Vaslin, B.
(2008). Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood
112: 4598-4608
[Abstract]
[Full Text]
-
Iannello, A., Debbeche, O., Samarani, S., Ahmad, A.
(2008). Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination. J. Leukoc. Biol.
84: 27-49
[Abstract]
[Full Text]
-
Diop, O. M., Ploquin, M. J.-Y., Mortara, L., Faye, A., Jacquelin, B., Kunkel, D., Lebon, P., Butor, C., Hosmalin, A., Barre-Sinoussi, F., Muller-Trutwin, M. C.
(2008). Plasmacytoid Dendritic Cell Dynamics and Alpha Interferon Production during Simian Immunodeficiency Virus Infection with a Nonpathogenic Outcome. J. Virol.
82: 5145-5152
[Abstract]
[Full Text]
-
Wei, Q., Stallworth, J. W., Vance, P. J., Hoxie, J. A., Fultz, P. N.
(2006). Simian Immunodeficiency Virus (SIV)/Immunoglobulin G Immune Complexes in SIV-Infected Macaques Block Detection of CD16 but Not Cytolytic Activity of Natural Killer Cells.. CVI
13: 768-778
[Abstract]
[Full Text]
-
Onanga, R., Souquiere, S., Makuwa, M., Mouinga-Ondeme, A., Simon, F., Apetrei, C., Roques, P.
(2006). Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills (Mandrillus sphinx).. J. Virol.
80: 3301-3309
[Abstract]
[Full Text]
-
Mavilio, D., Benjamin, J., Kim, D., Lombardo, G., Daucher, M., Kinter, A., Nies-Kraske, E., Marcenaro, E., Moretta, A., Fauci, A. S.
(2005). Identification of NKG2A and NKp80 as specific natural killer cell markers in rhesus and pigtailed monkeys. Blood
106: 1718-1725
[Abstract]
[Full Text]
-
Biassoni, R., Fogli, M., Cantoni, C., Costa, P., Conte, R., Koopman, G., Cafaro, A., Ensoli, B., Moretta, A., Moretta, L., De Maria, A.
(2005). Molecular and Functional Characterization of NKG2D, NKp80, and NKG2C Triggering NK Cell Receptors in Rhesus and Cynomolgus Macaques: Monitoring of NK Cell Function during Simian HIV Infection. J. Immunol.
174: 5695-5705
[Abstract]
[Full Text]
-
Hodara, V. L., Velasquillo, M. C., Parodi, L. M., Giavedoni, L. D.
(2005). Expression of CD154 by a Simian Immunodeficiency Virus Vector Induces Only Transitory Changes in Rhesus Macaques. J. Virol.
79: 4679-4690
[Abstract]
[Full Text]
-
Gomez-Roman, V. R., Patterson, L. J., Venzon, D., Liewehr, D., Aldrich, K., Florese, R., Robert-Guroff, M.
(2005). Vaccine-Elicited Antibodies Mediate Antibody-Dependent Cellular Cytotoxicity Correlated with Significantly Reduced Acute Viremia in Rhesus Macaques Challenged with SIVmac251. J. Immunol.
174: 2185-2189
[Abstract]
[Full Text]
-
Golub, M. S., Hogrefe, C. E., Germann, S. L., Jerome, C. P.
(2004). Endocrine Disruption in Adolescence: Immunologic, Hematologic, and Bone Effects in Monkeys. Toxicol Sci
82: 598-607
[Abstract]
[Full Text]
-
Van Rompay, K. K. A., Singh, R. P., Pahar, B., Sodora, D. L., Wingfield, C., Lawson, J. R., Marthas, M. L., Bischofberger, N.
(2004). CD8+-Cell-Mediated Suppression of Virulent Simian Immunodeficiency Virus during Tenofovir Treatment. J. Virol.
78: 5324-5337
[Abstract]
[Full Text]
-
Mavilio, D., Benjamin, J., Daucher, M., Lombardo, G., Kottilil, S., Planta, M. A., Marcenaro, E., Bottino, C., Moretta, L., Moretta, A., Fauci, A. S.
(2003). Natural killer cells in HIV-1 infection: Dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates. Proc. Natl. Acad. Sci. USA
100: 15011-15016
[Abstract]
[Full Text]
-
Benlhassan-Chahour, K., Penit, C., Dioszeghy, V., Vasseur, F., Janvier, G., Riviere, Y., Dereuddre-Bosquet, N., Dormont, D., Le Grand, R., Vaslin, B.
(2003). 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.
77: 12479-12493
[Abstract]
[Full Text]
-
Abel, K., Compton, L., Rourke, T., Montefiori, D., Lu, D., Rothaeusler, K., Fritts, L., Bost, K., Miller, C. J.
(2003). Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses. J. Virol.
77: 3099-3118
[Abstract]
[Full Text]
-
Lerche, N. W., Osborn, K. G.
(2003). Simian Retrovirus Infections: Potential Confounding Variables in Primate Toxicology Studies. Toxicol Pathol
31: 103-110
[Abstract]
-
Ahmad, R., Sindhu, S. T. A., Toma, E., Morisset, R., Ahmad, A.
(2002). Elevated Levels of Circulating Interleukin-18 in Human Immunodeficiency Virus-Infected Individuals: Role of Peripheral Blood Mononuclear Cells and Implications for AIDS Pathogenesis. J. Virol.
76: 12448-12456
[Abstract]
[Full Text]
-
Hakata, Y., Yamada, M., Mabuchi, N., Shida, H.
(2002). The Carboxy-Terminal Region of the Human Immunodeficiency Virus Type 1 Protein Rev Has Multiple Roles in Mediating CRM1-Related Rev Functions. J. Virol.
76: 8079-8089
[Abstract]
[Full Text]
-
Abel, K., Alegria-Hartman, M. J., Rothaeusler, K., Marthas, M., Miller, C. J.
(2002). The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-{alpha}/{beta}) and IFN-{alpha}/{beta}-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection. J. Virol.
76: 8433-8445
[Abstract]
[Full Text]
-
Forthal, D. N., Landucci, G., Daar, E. S.
(2001). Antibody from Patients with Acute Human Immunodeficiency Virus (HIV) Infection Inhibits Primary Strains of HIV Type 1 in the Presence of Natural-Killer Effector Cells. J. Virol.
75: 6953-6961
[Abstract]
[Full Text]
-
Iwanami, N., Niwa, A., Yasutomi, Y., Tabata, N., Miyazawa, M.
(2001). Role of Natural Killer Cells in Resistance against Friend Retrovirus-Induced Leukemia. J. Virol.
75: 3152-3163
[Abstract]
[Full Text]
-
Kornbluth, R. S.
(2000). The emerging role of CD40 ligand in HIV infection. J. Leukoc. Biol.
68: 373-382
[Abstract]
[Full Text]