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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-
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.
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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