K. D. Chavin

Prolongation of allograft and xenograft survival in mice by anti-CD2 monoclonal antibodies

&NA; Anti-CD2 monoclonal antibodies (mAb) were used to influence graft survival in two transplantation models. Xenogeneic rat islets were transplanted intraportally into mice. Anti-CD2 mAb prolonged xenograft survival and was synergistic with UVB irradiation in prolonging survival. Anti-CD2 mAb was also more potent than an anti-CD4 mAb in this model. Allogeneic cardiac grafts were transplanted across an entire H-2 difference and anti-CD2 mAb prolonged allograft survival in a dose-dependent fashion. Kinetic experiments revealed that anti-CD2 mAb was most potent when administered at the time of allografting. A delay in administration of mAb markedly reduced its immunosuppressive effects. Furthermore, additional doses of mAb given after the initial doses provided no increased immunosuppression and anti-CD2 mAbs did not delay rejection of secondset allografts. These findings support the notion that anti-CD2 mAbs interfere with afferent immunity and that CD2 is most important during the initial steps of an immune response. Investigation of the effect of anti-CD2 mAb on cellular immune functions demonstrated, in agreement with previous results, that it caused antigenic down-modulation of CD2 with relative sparing of CD3, CD4, and CD8 cell surface expression. Concommitantly the MLR, CTL, and NK responses were suppressed.

Inhibition of macrophage-activating cytokines is beneficial in the acute septic response.

Interferon-gamma and other cytokines enhance macrophage (M phi) antimicrobial function and have been considered for therapeutic use in sepsis. Systemic sequelae of macrophage activation, however, are unclear. This study examined the effects of M phi activating cytokines (interferon-gamma [IFN-gamma] and interleukin-4 [IL-4]) and monoclonal antibodies directed against these cytokines in modulating the acute septic response. CFW/Swiss Webster mice (n = 345) received endotoxin (lipopolysaccharide [LPS]: 60 mg/kg body weight intraperitoneally) and were randomized to five treatment groups: IFN-gamma (10(4) units), IL-4 (10(4) units), IgG1 isotype antibody (TRFK5: 200 micrograms), anti-IFN-gamma (200 micrograms), or anti-IL-4 (200 micrograms) monoclonal antibodies (MAbs) given simultaneously or 2 hours after LPS. Animals were divided into two groups and studied for mortality or measurement of peritoneal M phi superoxide anion release (O2-), tumor necrosis factor (TNF), and IL-6 production 6 hours after administration of LPS +/- experimental regimens. Serum TNF and IL-6 also were assessed at 2 and 4 hours after LPS, respectively. Administration of LPS resulted in a 27% survival compared with 10% in the IFN-gamma and 13% in the IL-4 groups. Treatment with anti-IFN-gamma offered protection against LPS lethality (93%-100% survival, p less than 0.001 vs. other groups) when given either simultaneously or 2 hours after LPS. Anti-IFN-gamma also significantly decreased PM phi O-2 and TNF release. Thus anti-IFN-gamma may have an important role in the modulation of the acute septic response.

Right atrial compression due to diaphragmatic eventration after liver transplantation: Successful treatment by diaphragmatic plication

Unilateral paralysis of the right hemidiaphragm after liver transplantation has a reported incidence of 30% to 40%. The mechanism of injury is most often a crush injury to the phrenic nerve due to the application of a suprahepatic inferior vena cava clamp. Most patients who suffer diaphragmatic paralysis at the time of transplantation never develop symptoms. Eventration of the right hemidiaphragm after liver transplantation causing right atrial compression and hemodynamic changes, to our knowledge, has not previously been reported.

Production of multiple murine CD2 receptor constructs using the baculovirus expression vector and a rapid dot-blot assay.

The baculovirus expression system was used to produce three different constructs of the murine cell surface adhesion receptor CD2. One construct coded for a single, N-terminal, Ig-fold domain. It was inefficiently secreted and therefore primarily intracellular. The second construct coded for both extracellular, N-terminal Ig-fold domains. This was efficiently secreted into culture supernatant. The third construct coded for the full-length transmembrane molecule which localized to the cell surface. All constructs were monomers of predicted MWr and were appropriately glycosylated. They retained epitopic specificity as demonstrated by binding to mAbs, and adhesion function as demonstrated by a rosetting assay.