Generation of agammaglobulinaemic mice by prenatal and postnatal exposure to polyclonal or monoclonal anti-IgM antibodies.

Improved experimental conditions are described for the treatment of mice with anti-IgM antibody, which subsequently lead to B-cell deficiency and agammaglobulinaemia. Antibody transmitted via maternal milk alone was found to be more efficient in inducing suppression of serum immunoglobulin isotypes than prenatal transmission or postnatal intraperitoneal injections alone. However, the combined treatment by all three routes of exposure to anti-IgM resulted in total B-cell suppression associated with undetectable levels of all serum immunoglobulin isotypes.

Immunity to lymphocytic choriomeningitis virus in B cell-depleted mice: evidence for B cell and antibody-independent protection by memory T cells.

Immunity against lymphocytic choriomeningitis virus (LCMV) in anti-IgM-treated B cell-depleted mice was evaluated. We found that the following immune phenomena were independent of antibodies: the generation of virus-specific cytotoxic T cells; the footpad swelling response against locally injected LCMV; natural killer cell activity basic levels or after LCMV or poly(I) X poly(C) stimulation; immunopathologically mediated LCM after primary intracerebral inoculation; immunological memory in LCMV-immune mice assessed by immune protection against LCM after intracerebrally injected virus or as resistance against the local footpad swelling response to LCMV. This study demonstrates that humoral immunity plays no crucial role in immune protection and immunopathology in murine LCMV infection and suggests that protective memory T cell function is B cell and antibody independent.

Effects of cyclosporin A on humoral immune response and resistance against vesicular stomatitis virus in mice.

The effect of cyclosporin A (CS-A) on the antiviral humoral response was studied by using vesicular stomatitis virus (VSV); VSV provided the opportunity to simultaneously assess both T-independent and T-dependent antibody responses. The T-independent anti-VSV immunoglobulin M (IgM) response was virtually unaffected, whereas the T-dependent primary anti-VSV IgG response was suppressed by CS-A; in contrast, the secondary IgG response was highly resistant to CS-A. Moreover, once the switch from IgM to IgG had occurred, the primary response also became refractory to suppression by CS-A.

Suppressive effects of B-lactam-antibiotics on in vitro generation of cytotoxic T-cells.

The in vitro effect of several compounds containing the B-lactam structure (including 6-aminopenicillanic acid, piperacillin, 7-aminocephalosporanic acid, ceftazidime and clavulanic acid) on the generation of cytotoxic lymphocytes was investigated in two different in vitro systems: (1) generation of virus specific cytotoxic T-cells and (2) proliferation of lymphocytes were assessed in secondary in vitro anti-viral immune responses. Both activities were suppressed by B-lactams in a dose-dependent manner. In these experiments, as found previously with human in vitro granulopoesis and proliferation of the human erythroleukaemic cell line K-562, cephalosporins and clavulanic acid were five to twenty times more suppressive than penicillins.

Suppression by cyclosporin A of murine T-cell-mediated immunity against viruses in vivo and in vitro.

The immunosuppressive effect of Cyclosporin A on T-cell-mediated antiviral immune responses was examined. When administered intraperitoneally CS-A abrogated anti-vaccinia virus, anti-lymphocytic choriomeningitis virus (LCMV), and anti-vesicular stomatitis virus (VSV) T-cell responses in a dose-dependent fashion. Usually 50-60 mg/kg were efficient in suppressing primary T-cell responses completely.