The role of CD4+ cells in vivo on the induction of the immune response to Porphyromonas gingivalis in mice.

BACKGROUND

It has previously been suggested that CD4+ T cells play a pivotal role in regulating the immune response to periodontal pathogens. The aim of the present study therefore was to determine delayed type hypersensitivity (DTH), spleen cell proliferation, serum and splenic anti-Porphyromonas gingivalis antibody levels, and lesion sizes following challenge with viable P. gingivalis in CD4-depleted BALB/c mice immunized with P. gingivalis outer membrane proteins (OMP).

METHODS

Four groups of BALB/c mice were used. Groups 1 and 2 were injected intraperitoneally (ip) with saline for 3 consecutive days and then weekly throughout the experiment. Groups 3 and 4 were injected ip with rat immunoglobulin and a monoclonal rat anti-mouse CD4 antibody, respectively. Two days later, group 1 mice were injected ip with saline only, while all the other groups were immunized ip with P gingivalis OMP weekly for 3 weeks. One week later following the last immunization of OMP, 3 separate experiments were conducted to determine: 1) the DTH response to P gingivalis OMP by measuring footpad swelling; 2) the levels of antibodies to P gingivalis in serum samples and spleen cell cultures using an enzyme-linked immunosorbent assay, as well as spleen cell proliferation after stimulation with OMP; and 3) the lesion sizes after a subcutaneous challenge with viable P. gingivalis cells.

RESULTS

In CD4+ T-cell-depleted mice (group 4), the DTH response and antigen-stimulated cell proliferation were significantly suppressed when compared to groups 2 and 3. Similarly, the levels of serum and splenic IgM, IgG, and all IgG subclass antibodies to P. gingivalis OMP were depressed. Delayed healing of P gingivalis-induced lesions was also observed in the CD4+ T-cell-depleted group.

CONCLUSIONS

This study has shown that depletion of CD4+ T cells prior to immunization with P gingivalis OMP led to the suppression of both the humoral and cell-mediated immune response to this microorganism and that this was associated with delayed healing. These results suggest that the induction of the immune response to P. gingivalis is a CD4+ T-cell-dependent mechanism and that CD4+ T cells are important in the healing process.