Human primary immune response in SCID mice engrafted with human peripheral blood lymphocytes.

Abstract

Severe combined immune deficient (SCID) mice were engrafted with human peripheral blood lymphocytes (Hu-PBLs) after treatment with anti-asialo GM-1 antiserum and radiation. This pretreatment facilitates high level of Hu-PBL engraftment in the SCID mice spleen. The next day, the Hu-PBL-SCID mice were immunized with either keyhole limpet hemocyanin (KLH), or carbohydrate Ag STn (AcNeu-alpha 2-alpha 6-Gal NAc-0) conjugated to KLH or protein of circumsporozoite malaria parasite (CSP), in a mixture of complete and incomplete Freund's adjuvant (1:10 v/v). The mice were bled 14 to 16 days after immunization, and the sera analyzed for STn-, KLH-, and CSP-specific human IgG and IgM Abs. The results showed that the immunized animals had a significantly higher titer of Ag-specific human IgG and IgM Abs compared to the control Hu-PBL-SCID mice. No significant Ab cross-reactions were detected between sera from KLH-, STn-, and CSP-vaccinated Hu-PBL-SCID mice. Depletion of either human CD4+ or CD8+ cells, in Hu-PBL-SCID mice, showed that CD4+ cells were essential for the primary immune response, but depletion of CD8+ cells had no influence on the titer of Ag-specific human IgG and IgM Abs.