CD40 LIGAND IS REQUIRED FOR RESOLUTION OF PNEUMOCYSTIS-CARINII PNEUMONIA IN MICE

The role of the CD40-CD40 ligand (CD40L) interaction in resolution of Pneumocystis carinii(PC) pneumonia (PCP) was assessed in a PC-infected severe combined immunodeficiency (SCID) mouse reconstitution model us ing an anti-CD40L mAb to block CD40L. SCID mice infected with PC were reconstituted with unfractionated spleen cells from immunocompetent do nors and given either anti-CD40L mAb or an irrelevant control mAb. Mic e given the control mAb resolved the PC infection, whereas those given the anti-CD40L mAb did not. That anti-CD40L mAb also inhibited PC-spe cific IgG production is consistent with the possibility that cognate C D4(+) T cell-B cell interactions are important in PCP resolution, The experiment was then repeated, except that the PC-infected SCID mice we re reconstituted with purified CD4(+) T cells only, Again, the control mAb-treated group resolved the PCP, whereas mice treated with anti-CD 40L mAb did not. In the second experiment, inhibition of resolution of PCP in the anti-CD40L mAb group was not the result of blocking CD4(+) T cell-dependent activation of PC-specific B cells. The results are c onsistent with the possibility that resistance to PCP may involve inte raction between B cells and CD4(+) T cells via the CD40-CD40L pathway. However, results additionally indicate that inhibition of CD40-CD40L interaction ablates resistance to PCP by inhibiting the interaction of T cells with some cell other than B cells.