PROTECTION AGAINST PNEUMOCYSTIS-CARINII PNEUMONIA BY ANTIBODIES GENERATED FROM EITHER T-HELPER-1 OR T-HELPER-2 RESPONSES

To determine whether different antibody isotypes associated with T hel per 1 (Th1) or Th2 responses are protective against Pneumocystis carin ii, mice with disrupted interleukin 4 genes (IL-4(-/-) mice) or gamma interferon genes (IFN-gamma(-/-) mice) along with wild-type C57BL/6 mi ce were immunized intratracheally against P. carinii, depleted of T ce lls in vivo by use of monoclonal antibodies, and rechallenged intratra cheally with 10(7) viable P. carinii organisms, Nearly all immunized m ice resolved their lung P. carinii infections (limit of detection, log (10) 4.06) within 21 days of challenge even though they were depleted of T cells. Unimmunized mice depleted of T cells had significant lung infections (>log(10) 5.5) at day 21 post-P. carinii challenge. IFN-gam ma(-/-) and wild-type mice developed P. carinii-specific immunoglobuli n primarily of the immunoglobulin G1 (IgG1) subclass with relatively l ittle P. carinii-specific IgG2a, IgG2b, or IgG3 in their sera, charact eristic of a Th2-type response. In contrast, IL-4(-/-) mice had primar ily an IgG2b P. carinii-specific antibody response in their sera with very little IgG1. Although IgG2b was the predominant isotype in IL-4(- /-) mice, optical density values of IgG2a and IgG3 were significantly higher in these mice (two and three times, respectively) than in IFN-g amma(-/-) mice, characteristic of a Th1-type response, Together, these data indicate that resolution of P. carinii infection can be mediated by specific antibody responses and that the antibody response can be either a predominantly Th1 or Th2 type. Furthermore, although wild-typ e mice mounted a Th2-like antibody response, IL-4(-/-) mice could reso lve P. carinii pneumonia, indicating that resistance to P. carinii can occur in the absence of IL-4.