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Inhibition of human antigen-specific memory B cell response in vitro by a diphtheria toxin-related interleukin 2 fusion protein.

Authors
  • Grailer, A P
  • Nichols, J C
  • Strom, T B
  • Sollinger, H W
  • Burlingham, W J
Type
Published Article
Journal
Cellular immunology
Publication Date
Feb 01, 1991
Volume
132
Issue
2
Pages
481–493
Identifiers
PMID: 1988163
Source
Medline
License
Unknown

Abstract

Recombinant diphtheria toxin-related interleukin-2 fusion protein (DAB486IL-2) is specifically cytotoxic for cells bearing the high-affinity IL-2 receptor (p55/75). We evaluated the effects of DAB486IL-2 on the generation of tetanus toxoid (TT)-specific IgG antibody-forming cells in 6-day cocultures of human splenocytes and TT-coupled Sepharose beads. The results indicate that a significant portion (30-75%) of the anti-tetanus toxoid IgG response in vitro was susceptible to inhibition by 10(-10) M DAB486IL-2. The inhibition required both the IL-2 portion of the fusion protein and an active toxin moiety and was greater when the IL-2 toxin was added on Day 3 as compared with Day 0 of culture. The induction of the p55 (Tac) subunit of the IL-2R was demonstrable by two-color flow cytometry on a small percentage (5%) of B cells and on a higher percentage (10%) of non-B cells 3 days after exposure to TT-coupled Sepharose. Short-term (2 hr) treatment of T and B cell subpopulations separated on Day 3 of culture followed by remixing indicated that while activated T helper cells were most strongly inhibited by DAB486IL-2, up to 50% of the TT-specific IgG response was inhibited by treatment of B cells alone with DAB486IL-2. Our results suggest that a strategy of eliminating human memory B cells by a combination of antigen activation and properly timed administration of a recombinant lymphokine-toxin fusion protein is feasible.

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