Mice infected with Schistosoma mansoni develop a novel non-T-lymphocyte suppressor population which inhibits virus-specific CTL induction via a soluble factor.
We previously observed that Schistosoma mansoni-infected mice were deficient in their ability to mount a CTL response to unrelated viral antigens and to clear a vaccinia viral infection. Here, we explore the mechanism of that deficiency. Mixing experiments showed that splenocytes from S. mansoni-infected mice actively suppress stimulation in vitro of both viral-peptide specific CTL in spleen cells from virus-infected mice, and allospecific CTL. The mechanism of suppression involves at least in part a soluble factor, in that it can occur across a 0.4-microm membrane which prohibits direct cell contact. However, the inhibition is not alleviated by blocking with antibodies to IL-4, IL-10 or TGF-beta. Fractionation of the splenocyte population from S. mansoni-infected mice shows that the suppression is mediated by a non-B, non-T cell that expresses CD16 and Mac-1, but not FcepsilonR or NK1.1. This represents a novel suppressor population that is distinct from the FcepsilonRI(+) populations of non-B, non-T cells in the spleens of S. mansoni-infected mice that provide a major source of IL-4 in these animals. Similar cells in schistosome-infected humans could affect susceptibility to other infections or responsiveness to vaccines.
Marshall
M A
MA
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Building 10, Room 6B-12, NIH, Bethesda, MD 20892, USA.
Jankovic
D
D
Maher
V E
VE
Sher
A
A
Berzofsky
J A
JA
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014616:Vaccinia virus / Q000235:genetics
D000941:Antigens; D013491:Suppressor Factors, Immunologic; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4