Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice.
Oral inoculation of BALB/c mice with infective larvae of Heligmosomoides polygyrus resulted in chronic infection characterized by the release of parasite eggs in the feces for several months. The actual number of eggs per gram of feces was dependent on the dose of the inoculum. Serum IgE in infected mice peaked at a level of greater than 70 micrograms/ml during Weeks 3 through 6 following inoculation, and high levels of IgE (greater than 40 micrograms/ml) persisted for over 14 weeks. Protective immune responses resulted in reduced egg production and the development of markedly fewer adult worms in the small intestines following a challenge inoculation. The role of CD4+ and CD8+ T cells in these responses was examined by depletion in vivo of either T cell subpopulation with rat mAb specific for the appropriate determinants. Mice treated with anti-CD4 during a primary infection had increased EPG which was due primarily to an increase in worm fecundity (eggs produced per adult female). A challenge inoculation of mice that had been cleared of the primary infection with an anthelmintic drug induced a protective response that reduced development of new adult worms by 70-80% and their fecundity by greater than 90%. This protective response was abrogated by injection of mice with anti-CD4. Serum IgE diminished when adult worms were removed after anthelmintic treatment. A more precipitous drop in serum IgE followed successive treatments of mice with an anthelmintic and anti-CD4. In addition, the anamnestic serum IgE response to a challenge inoculation was reduced by over 80% in anti-CD4-treated mice. Anti-CD8 treatment had no appreciable effect on the immunological or parasitological parameters measured following a challenge inoculation with H. polygyrus. Thus, CD4+ T cells regulate host protective immunity, worm fecundity, and IgE levels in an H. polygyrus infection. This experimental system may be particularly suitable for analysis of chronic nematode infections of humans and livestock because of the responsiveness of the parasite in vivo to changes in host immune function.
Helminthic Diseases Laboratory, Livestock and Poultry Sciences Institute, U.S. Department of Agriculture, Beltsville, Maryland 20705-2350.
J F
JF
Urban
I M
IM
Katona
F D
FD
Finkelman
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D005260:Female; D007110:Immunity, Active; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009349:Nematode Infections / Q000276:immunology* / Q000469:parasitology; D009351:Nematospiroides dubius / Q000276:immunology* / Q000502:physiology; D010270:Parasite Egg Count; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000906:Antibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D007074:Immunoglobulin G; D007073:Immunoglobulin E