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 using an anti-CD40L mAb to block CD40L. SCID mice infected with PC were reconstituted with unfractionated spleen cells from immunocompetent donors and given either anti-CD40L mAb or an irrelevant control mAb. Mice given the control mAb resolved the PC infection, whereas those given the anti-CD40L mAb did not. That anti-CD40L mAb also inhibited PC-specific IgG production is consistent with the possibility that cognate CD4+ T cell-B cell interactions are important in PCP resolution. The experiment was then repeated, except that the PC-infected SCID mice were reconstituted with purified CD4+ T cells only. Again, the control mAb-treated group resolved the PCP, whereas mice treated with anti-CD40L 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 consistent with the possibility that resistance to PCP may involve interaction 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.
Wiley
J A
JA
Trudeau Institute, Inc., Saranac Lake, NY 12983, USA.
Harmsen
A G
AG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D005434:Flow Cytometry; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D011010:Pneumocystis; D011020:Pneumonia, Pneumocystis / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D023201:CD40 Ligand