Effect of IL-12 and soluble IL-4 receptor on the herpesvirus infection in human SCID chimeras whose Th2 cells...

Th2 cytokines, commonly detected in burn patients, have been shown as inhibitors for the generation of Th1 cells that are essential for the host's resistance against herpes simplex virus type 1 (HSV-1) infection. In this study, the possibility of immunological treatment through the regulation of Th1/Th2 responses was examined in two kinds of human severe combined immunodeficiency (SCID) chimera models reflecting human immune functions. SCID mice injected with a mixture of PBMC from a healthy donor and Th2 cells experimentally generated from the same healthy PBMC (Th2 SCID chimeras) were more susceptible to HSV-1 infection when compared with SCID mice injected with healthy donor PBMC (healthy SCID chimeras). When Th2 SCID chimeras were individually treated with human IL-12 (hIL-12) or human soluble IL-4 receptor (hsIL-4R), hIFN-gamma was not produced in their sera after antihuman CD3 mAb stimulation. However, hIFN-gamma production in sera of Th2 SCID chimeras treated with the combination therapy of hIL-12 and hsIL-4R was recovered at levels observed in healthy SCID chimeras. When Th2 SCID chimeras infected with HSV-1 were treated with saline, hIL-12, hsIL-4R or a combination of hIL-12 and hsIL-4R, 13%, 13%, 25% or 100% of them survived, respectively. Also, Th1 responses (hIFN-gamma production) were demonstrated in Th2 SCID chimeras that became resistant against HSV-1 infection after the combination treatment. These results suggest that individuals whose Th2 cells predominated may be immunologically controlled by the combination treatment between a Th1 response inducer and a Th2 response inhibitor.