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J Gen Virol 75 (1994), 2789-2794; DOI 10.1099/0022-1317-75-10-2789
© 1994 Society for General Microbiology

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Defective response to T cell mitogens in mice injected with human immunodeficiency virus type 1-infected U937 cells

Clara M. Ausiello1, Paola Sestili2, Chiara Locardi2, Mariantonia Logozzi2, Paola Rizza2, Eleonora Parlanti2, Li-xia Yang2, Alessandro Modica3, Andrea Modesti3, Piero Musiani3, Thomas J. Kaido4, Carmela Rozera2, Stefano Buttò2 and Filippo Belardelli2,{dagger}

1 Laboratory of Bacteriology and Medical Mycology
and2 Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome
3 Department of Human Pathology, University of Chieti, Chieti, Italy,
and4 Laboratory of Viral Oncology, I.R.S.C., 94802, Villejuif, France

Swiss mice were injected intraperitoneally with uninfected or human immunodeficiency virus type 1 (HIV-1) infected human U937 cells. At 6 days, no residual human cells were detected in mouse tissues as determined by PCR analysis of DNAs from injected mice using primers and probes for the human HLA-DQ alpha gene. At 6 to 12 months, approximately 60% of the HIV-1-injected mice had antibodies to HIV-1 gp 120 and gp41 proteins. Fifteen percent of the animals showed evidence of HIV-1 infection as determined by PCR analyses of DNA from peripheral blood leukocytes and by in situ hybridization for detection of HIV-1 mRNA in peritoneal cells. In this set of experiments, spleen cells from mice sacrificed at different times after injection were cultured for 48 h in the presence or absence of mitogens [i.e.: concanavalin (Con A) or anti-CD3 antibody] and then tested for lymphocyte proliferation. At 10 to 12 months, splenocytes from approximately 80% of Swiss mice injected with HIV-1-infected U937 cells exhibited a marked defect in their proliferative response to Con A or anti-CD3 antibody as compared with spleen cells from both uninjected or U937 cell-injected mice. Similar results were obtained at 12 months in C3H/HeJ mice. Non-responding spleen cells from HIV-1-injected Swiss mice did not proliferate in response to anti-CD3 antibody even in the presence of co-stimulatory molecules such as phorbol myristate acetate or anti-CD28 antibody. Splenocytes from these mice also exhibited an impaired capacity to produce interferon-{gamma} and interleukin-4 after mitogen stimulation. No T cell defects were observed in control-injected mice. Immunofluorescence analyses revealed a significant decrease in the percentage of both CD4+ and CD8+ spleen cells in HIV-1-injected mice. These data indicate that immunocompetent mice can be used to investigate some HIV-1-related immune dysfunctions in vivo.

{dagger} We dedicate this article to the memory of our colleague and friend Professor Giovanni B. Rossi, who died on 20 February 1994.

Received 16 March 1994; accepted 24 May 1994.


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C. M. Ausiello, R. Lande, P. Stefanelli, C. Fazio, G. Fedele, R. Palazzo, F. Urbani, and P. Mastrantonio
T-Cell Immune Response Assessment as a Complement to Serology and Intranasal Protection Assays in Determining the Protective Immunity Induced by Acellular Pertussis Vaccines in Mice
Clin. Vaccine Immunol., July 1, 2003; 10(4): 637 - 642.
[Abstract] [Full Text] [PDF]




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