Persistent suppression of virus-specific cytotoxic T cell responses after transient depletion of CD4+ T cells in vivo

J. J. Goronzy, C. M. Weyand

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Co-administration of soluble Ag and anti-CD4 mAb has been successfully used to induce long term Ag-specific tolerance. The mechanisms underlying persistent immunologic unresponsiveness are unclear. We have now studied whether tolerance toward complex viral Ag expressed on Moloney sarcoma virus (MSV)-transformed tumor cells can be induced when given at the time of severe helper cell depletion. Although mice that had been injected with anti-CD4 mAb at the time of immunization regained the ability to recognize MSV Ag, their humoral and cytotoxic immunity to MSV were severely compromised. Ag-specific low responsiveness was maintained for more than 6 mo. To analyze the T cell repertoire of low responder mice we have estimated precursor frequencies of MSV-specific proliferative and cytotoxic T cells after the CD4+ T cell subset was fully reconstituted. There was no difference in the frequencies of control and low responder mice excluding clonal deletion as the mechanism maintaining low responsiveness. In co-culture experiments the defect in low responder mice could be localized to the regenerated CD4+ T cell subset, suggesting the induction of CD4+ suppressor-inducer cells. Alternatively, regenerated CD4+ cells in anti-CD4 conditioned mice had acquired a defect to provide help for MSV-specific responses. In spite of the potentials to induce low responsiveness to selected Ag by anti-CD4 conditioning, the risk to cause persistent virus-specific immunodeficiency might limit the clinical application of anti-CD4 therapy.

Original languageEnglish (US)
Pages (from-to)4435-4440
Number of pages6
JournalJournal of Immunology
Volume142
Issue number12
StatePublished - 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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