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BOR - Papers in Press, published online ahead of print July 7, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.029215
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BIOLOGY OF REPRODUCTION 71, 1638–1645 (2004)
DOI: 10.1095/biolreprod.104.029215
© 2004 by the Society for the Study of Reproduction, Inc.

Immunology

Effect of Candidate Vaginally-Applied Microbicide Compounds on Recognition of Antigen by CD4+ and CD8+ T Lymphocytes1

Gregg N. Milligan2,4,3, Chin-Fun Chu4,3, Christal G. Young4,3, and Lawrence R. Stanberry4,3

Sealy Center for Vaccine Development3 Department of Pediatrics,4 University of Texas Medical Branch-Galveston, Galveston, Texas 77555-0436

Vaginally applied antimicrobial compounds (microbicides) are being developed as an alternative method for preventing the spread of sexually transmitted diseases. In addition to identifying compounds effective against a spectrum of sexually transmitted pathogens, it will be important to ensure that these compounds are safe. Avoiding toxicity, inflammatory responses, or alteration of the function of resident immune cells are important considerations for the development of vaginally applied microbicides. Studies were performed with two classes of candidate microbicide compounds to determine if they would interfere with the recognition of antigen by CD4+ and CD8+ T lymphocytes. The presence of nontoxic concentrations of the anionic detergent cholic acid or the sulfated polymer lambda carrageenan did not inhibit recognition of immune peptide by antigen-specific T cells. However, antigen recognition by both CD4+ and CD8+ T lymphocytes was inhibited in the presence of the naphthalene sulfonate polymer PRO 2000. Brief (4-h) exposure of antigen-presenting cells or T cells to PRO 2000 did not result in inhibition of antigen uptake and processing by antigen-presenting cells or the ability of specific T cells to respond to antigen stimulation, suggesting that the inhibition was temporary. Binding of antibodies specific for CD18, CD8, and CD3 was impaired in the presence of PRO 2000, suggesting that the mechanism by which this microbicide inhibits T cell recognition of antigenic peptide may involve masking or internalization of surface proteins involved in T cell signaling or stabilizing T cell-antigen-presenting cell interactions. The assays described in this study represent a useful means to screen candidate topical microbicide compounds for inappropriate interactions with immune cells and may be useful for prioritization of candidate microbicide compounds.

1 Supported by research grants AI-37940, AI-42815, and AI-054444 from the National Institutes of Health.

2 Correspondence: Gregg N. Milligan, Sealy Center for Vaccine Development, 301 University Blvd., Galveston, TX 77555-0436. FAX: 409 747 8150; gnmillig{at}utmb.edu






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Copyright © 2004 by the Society for the Study of Reproduction.