T cells and natural killer cells regulate human IgG subclass concentrations in SCID mice.

Cytokine regulation of human IgG subclass production is not well understood. Since T cells and natural killer (NK) cells produce IL-4 and/or IFN-gamma, we examined the effect of these cells on human IgG subclass concentration in reconstituted severe combined immunodeficient (SCID) mice. SCID mice receiving only B-cell-enriched splenocyte preparations had significantly decreased IgG concentrations and significantly decreased IgG1/IgG2 ratios compared to mice receiving B cells plus T cells (P = 0.02). IgG2 represented 58% of the total IgG at 28 days in mice receiving B-cell-enriched preparations compared to 19% of the total for the group receiving both B cells and T cells (P = 0.013). The effect of natural killer cells (CD16+) on IgG subclass was also studied in this model. IgG2 concentrations were twofold higher in mice receiving CD16-depleted cells compared to controls (P = 0.004). No significant differences were noted for IgG1, IgG3, or IgG4 subclass concentrations. In conclusion, T cells and natural killer cells influence human IgG subclass regulation in the SCID mouse model. We propose that the regulation of human IgG subclass production can be further examined in the SCID model.

IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in young infants.

PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti-HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC.