Inhibition of DNA synthesis and IL-2 bioactivity in MLR by splenic pregnancy-associated natural suppressor cells involves the production of a TGF-β1-like molecule and a second distinct inhibitory factor

Jane C. Brooks-Kaiser, David W. Hoskin

Résultat de recherche: Articleexamen par les pairs

13 Citations (Scopus)

Résumé

Natural suppressor cells exhibiting a double-negative, immature T cell phenotype have been identified in maternal spleen during syngeneic murine pregnancy. In the present study, splenic pregnancy-associated natural suppressor (SPANS) cells are shown to express α/β T cell receptors. SPANS cell-mediated inhibition of DNA synthesis by spleen cells responding in mixed lymphocyte reactions (MLR) is associated with a reduction in interleukin (IL)-2 bioactivity beginning after 96 h of culture. Although culture supernatants from suppressed MLR exhibit diminished ability to support the growth of IL-2-dependent CTLL-2 cells, SPANS cells themselves are unable to inhibit IL-2-driven CTLL-2 proliferation, suggesting that SPANS cells down-regulate IL-2 synthesis in MLR. IL-2 utilization in MLR is also inhibited by SPANS cells, since the addition of exogenous IL-2 fails to relieve the inhibitory effect of SPANS cells on lymphoproliferative responses in MLR. Flow cytofluorometric analysis reveals that MLR performed in the presence of SPANS cells contain normal percentages of CD4 and IL-2 receptor-bearing spleen cells. Thus, SPANS cells do not inhibit cellular proliferation in MLR by selectively interfering with clonal expansion of IL-2-producing helper T cells or by down-regulating IL-2 receptor expression. We have determined that SPANS cells inhibit DNA synthesis in MLR via the production of a transforming growth factor (TGF)-β1-like suppressor factor, since cellular proliferation in MLR is restored to normal levels in the presence of anti-TGF-β1 neutralizing antibody. However, IL-2 bioactivity in these cultures.

Langue d'origineEnglish
Pages (de-à)31-49
Nombre de pages19
JournalJournal of Reproductive Immunology
Volume25
Numéro de publication1
DOI
Statut de publicationPublished - sept. 1993

Note bibliographique

Funding Information:
This work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada. The authors wish to thank Linda Best for flow cytofluorometric analysis. Jane Brooks-Kaiser is the recipient of a Medical Research Council of Canada studentship and an Izaak Walton Killam Memorial graduate scholarship.

ASJC Scopus Subject Areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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