Defective response to T cell mitogens in mice injected with human immunodeficiency virus type 1-infected U937 cells.
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-infected 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.
Ausiello
C M
CM
Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy.
Sestili
P
P
Locardi
C
C
Logozzi
M
M
Rizza
P
P
Parlanti
E
E
Yang
L
L
Modica
A
A
Modesti
A
A
Musiani
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D017690:Cell Transplantation; D003208:Concanavalin A; D017931:DNA Primers; D015699:HIV Envelope Protein gp120 / Q000032:analysis / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014181:Transplantation Immunology
D000906:Antibodies; D017252:CD3 Complex; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; D015345:Oligonucleotide Probes; D003208:Concanavalin A; D015847:Interleukin-4