The Journal of Immunology, Vol 157, Issue 6 2712-2718, Copyright © 1996 by American Association of Immunologists

ARTICLES

Single cell analysis of IL-4 and IFN-gamma production by T cells from HIV-infected individuals: decreased IFN-gamma in the presence of preserved IL-4 production

L Meyaard, E Hovenkamp, IP Keet, B Hooibrink, IH de Jong, SA Otto and F Miedema
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.

The specific in vitro disturbance of capacities ascribed to Th1 cells in HIV-infected individuals suggests a switch from Th1 to Th2 lymphokine secretion. Indeed, when T cell clones are generated from HIV- infected individuals compared with controls, an increased percentage of Th0 clones is present upon HIV infection. We studied cytokine production in the supernatant of in vitro activated PBMC from a large group of HIV-infected patients at various stages of infection. IL-2, IFN-gamma, IL-4, IL-5, and IL-10 production all were decreased significantly, which does not support a switch to Th2 lymphokine secretion and is possibly due to the generalized impaired response of T cells from HIV-infected individuals to activation signals in vitro. Therefore, we investigated the capacity of single cells to produce a certain cytokine. Intracellular staining of IL-4- and IFN-gamma- producing cells revealed that T cells from HIV-infected individuals contained decreased numbers of IFN-gamma-producing cells, in the presence of normal percentages of cells with the capacity to produce IL- 4. This resulted in significantly decreased IFN-gamma/IL-4 ratios in both CD4+ and CD8+ T cells. Thus, in agreement with previous findings in T cell clones, we conclude, from cytokine production upon stimulation of T cells in vitro, that there is a change in the cytokine balance to the Th2 side in HIV infection due to decreased Th1 and preserved Th2 cytokine production.

This article has been cited by other articles:

				D. A. Kosub, G. Lehrman, J. M. Milush, D. Zhou, E. Chacko, A. Leone, S. Gordon, G. Silvestri, J. G. Else, P. Keiser, et al. Gamma/Delta T-Cell Functional Responses Differ after Pathogenic Human Immunodeficiency Virus and Nonpathogenic Simian Immunodeficiency Virus Infections J. Virol., February 1, 2008; 82(3): 1155 - 1165. [Abstract] [Full Text] [PDF]

				G. R. de Arquer, R. Pena, C. Cabrera, G. Coma, R. Ruiz-Hernandez, R. Guerola, B. Clotet, L. Ruiz, J. A. Este, M. L. Calle, et al. Skewed expression and up-regulation of the IL-12 and IL-18 receptors in resting and activated CD4 T cells from HIV-1-infected patients J. Leukoc. Biol., July 1, 2007; 82(1): 72 - 78. [Abstract] [Full Text] [PDF]

				K. Gee, J. B. Angel, S. Mishra, M. A. Blahoianu, and A. Kumar IL-10 Regulation by HIV-Tat in Primary Human Monocytic Cells: Involvement of Calmodulin/Calmodulin-Dependent Protein Kinase-Activated p38 MAPK and Sp-1 and CREB-1 Transcription Factors J. Immunol., January 15, 2007; 178(2): 798 - 807. [Abstract] [Full Text] [PDF]

				L. Ramakrishna, K. K. Anand, K. M. Mohankumar, and U. Ranga Codon Optimization of the Tat Antigen of Human Immunodeficiency Virus Type 1 Generates Strong Immune Responses in Mice following Genetic Immunization J. Virol., September 1, 2004; 78(17): 9174 - 9189. [Abstract] [Full Text] [PDF]

				E. Ledru, M. Fevrier, H. Lecoeur, S. Garcia, S. Boullier, and M.-L. Gougeon A nonsecreted variant of interleukin-4 is associated with apoptosis: implication for the T helper-2 polarization in HIV infection Blood, April 15, 2003; 101(8): 3102 - 3105. [Abstract] [Full Text] [PDF]

				D. Creery, J. B. Angel, S. Aucoin, W. Weiss, W. D. Cameron, F. Diaz-Mitoma, and A. Kumar Nef Protein of Human Immunodeficiency Virus and Lipopolysaccharide Induce Expression of CD14 on Human Monocytes through Differential Utilization of Interleukin-10 Clin. Vaccine Immunol., November 1, 2002; 9(6): 1212 - 1221. [Abstract] [Full Text] [PDF]

				T. A. Reinhart, B. A. Fallert, M. E. Pfeifer, S. Sanghavi, S. Capuano III, P. Rajakumar, M. Murphey-Corb, R. Day, C. L. Fuller, and T. M Schaefer Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome Blood, May 1, 2002; 99(9): 3119 - 3128. [Abstract] [Full Text] [PDF]

				W. L. Chan, N. Pejnovic, C. A. Lee, and N. A. Al-Ali Human IL-18 Receptor and ST2L Are Stable and Selective Markers for the Respective Type 1 and Type 2 Circulating Lymphocytes J. Immunol., August 1, 2001; 167(3): 1238 - 1244. [Abstract] [Full Text] [PDF]

				S. HOWIE, R. RAMAGE, and T. HEWSON Innate Immune System Damage in Human Immunodeficiency Virus Type 1 Infection . Implications for Acquired Immunity and Vaccine Design Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S141 - 145. [Abstract] [Full Text] [PDF]

				M. De Brabander HIV-associated dysfunction of in vitro IL-12 production depends on the nature of the stimulus and on the CD4 T-cell count of the patient Blood, March 15, 2000; 95(6): 2185 - 2187. [Full Text] [PDF]

				J. D. Marshall, J. Chehimi, G. Gri, J. R. Kostman, L. J. Montaner, and G. Trinchieri The Interleukin-12-Mediated Pathway of Immune Events Is Dysfunctional in Human Immunodeficiency Virus-Infected Individuals Blood, August 1, 1999; 94(3): 1003 - 1011. [Abstract] [Full Text] [PDF]

				R. T. Bailer, A. Holloway, J. Sun, J. B. Margolick, M. Martin, J. Kostman, and L. J. Montaner IL-13 and IFN-{gamma} Secretion by Activated T Cells in HIV-1 Infection Associated with Viral Suppression and a Lack of Disease Progression J. Immunol., June 15, 1999; 162(12): 7534 - 7542. [Abstract] [Full Text] [PDF]

				M. M. Nociari, W. Telford, and C. Russo Postthymic Development of CD28-CD8+ T Cell Subset: Age-Associated Expansion and Shift from Memory to Naive Phenotype J. Immunol., March 15, 1999; 162(6): 3327 - 3335. [Abstract] [Full Text] [PDF]

				Y. Suzuki, Y. Koyanagi, Y. Tanaka, T. Murakami, N. Misawa, N. Maeda, T. Kimura, H. Shida, J. A. Hoxie, W. A. O'Brien, et al. Determinant in Human Immunodeficiency Virus Type 1 for Efficient Replication under Cytokine-Induced CD4+ T-Helper 1 (Th1)- and Th2-Type Conditions J. Virol., January 1, 1999; 73(1): 316 - 324. [Abstract] [Full Text] [PDF]

				J. L. Stinn, M. K. Taylor, G. Becker, H. Nagano, S. Hasegawa, Y. Furakawa, K. Shimizu, P. Libby, and R. N. Mitchell Interferon-{gamma}-Secreting T-Cell Populations in Rejecting Murine Cardiac Allografts : Assessment by Flow Cytometry Am. J. Pathol., November 1, 1998; 153(5): 1383 - 1392. [Abstract] [Full Text] [PDF]

				D. David, L. Bani, J.-L. Moreau, M.-P. Treilhou, T. Nakarai, M. Joussemet, J. Ritz, B. Dupont, G. Pialoux, and J. Theze Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy PNAS, September 15, 1998; 95(19): 11348 - 11353. [Abstract] [Full Text] [PDF]

				J. A. Mikovits, H. A. Young, P. Vertino, J.-P. J. Issa, P. M. Pitha, S. Turcoski-Corrales, D. D. Taub, C. L. Petrow, S. B. Baylin, and F. W. Ruscetti Infection with Human Immunodeficiency Virus Type 1 Upregulates DNA Methyltransferase, Resulting in De Novo Methylation of the Gamma Interferon (IFN-gamma ) Promoter and Subsequent Downregulation of IFN-gamma Production Mol. Cell. Biol., September 1, 1998; 18(9): 5166 - 5177. [Abstract] [Full Text]

				J. J. Mattapallil, Z. Smit-McBride, M. McChesney, and S. Dandekar Intestinal Intraepithelial Lymphocytes Are Primed for Gamma Interferon and MIP-1beta Expression and Display Antiviral Cytotoxic Activity despite Severe CD4+ T-Cell Depletion in Primary Simian Immunodeficiency Virus Infection J. Virol., August 1, 1998; 72(8): 6421 - 6429. [Abstract] [Full Text] [PDF]

				Z. Smit-McBride, J. J. Mattapallil, M. McChesney, D. Ferrick, and S. Dandekar Gastrointestinal T Lymphocytes Retain High Potential for Cytokine Responses but Have Severe CD4+ T-Cell Depletion at All Stages of Simian Immunodeficiency Virus Infection Compared to Peripheral Lymphocytes J. Virol., August 1, 1998; 72(8): 6646 - 6656. [Abstract] [Full Text] [PDF]

				A. Valentin, W. Lu, M. Rosati, R. Schneider, J. Albert, A. Karlsson, and G. N. Pavlakis Dual effect of interleukin 4 on HIV-1 expression: Implications for viral phenotypic switch and disease progression PNAS, July 21, 1998; 95(15): 8886 - 8891. [Abstract] [Full Text] [PDF]

				J. A. Mikovits, D. D. Taub, S. M. Turcovski-Corrales, and F. W. Ruscetti Similar Levels of Human Immunodeficiency Virus Type 1 Replication in Human TH1 and TH2 Clones J. Virol., June 1, 1998; 72(6): 5231 - 5238. [Abstract] [Full Text] [PDF]

				E. Ledru, H. Lecoeur, S. Garcia, T. Debord, and M.-L. Gougeon Differential Susceptibility to Activation-Induced Apoptosis Among Peripheral Th1 Subsets: Correlation with Bcl-2 Expression and Consequences for AIDS Pathogenesis J. Immunol., April 1, 1998; 160(7): 3194 - 3206. [Abstract] [Full Text] [PDF]