National Cancer Institute (NCI) researchers and their collaborators have developed a laboratory model, which uses skin tissue, that should serve as a reliable tool for testing agents used topically during sexual intercourse to fight off HIV infection. To date, no available tissue culture models have proven adequate for preclinical testing of these agents, called microbicides. In the absence of an effective AIDS vaccine, microbicides are being developed to help stem the worldwide spread of AIDS. The new model for testing microbicdes is described in the November 20, 2000, issue of the Journal of Experimental Medicine.*
The research was done in collaboration with scientists from the National Institute of Child Health and Human Development, Bethesda, Md.; George Washington University, Washington, D.C.; University of Geneva, Switzerland; and New York Blood Center, New York, N.Y. Researchers examined Langerhans' cells, which are found in the epidermal layer of human skin. These cells can become some of the first that can be infected by HIV during unprotected sexual intercourse.
Scientists in this study felt that Langerhans' cells were particularly worth studying because they can express CD4 and CCR5, known cell surface receptors for HIV which enable HIV to enter the body. It has been shown that a person who does not carry the CCR5 gene can be relatively protected from HIV infection despite repeated exposures to the virus. Langerhans' cells also transmit HIV to CD4 T-cells in the body, which can lead to drastic depletion of these immune cells in cases of full-blown AIDS.
According to the senior author of the paper, Andrew Blauvelt, M.D., of NCI's Dermatology Branch, "We found that our model was indeed very promising when two potential microbicides currently under investigation blocked both infection of Langerhans' cells and subsequent transmission of infection to T-cells."
Researchers trying to develop a potent microbicide hope to find one that is easy to use while also being stable and non-irritating in genital mucosal tissues. The ability of HIV to bind to and infect initial target cells such as Langerhans' cells represents a critical step in transmitting HIV during sexual intercourse. Blauvelt's model is of particular importance because it provides a means to identify agents that block this critical step.
Researchers developed their model by blistering human skin and then culturing it in laboratory dishes. By exposing the cultured skin to HIV, they were able to observe the infection of Langerhans' cells in skin as opposed to previous models that looked at individual cells in solution. Therefore, Blauvelt's model more likely mimics biologic conditions present during sexual transmission of HIV.
*The authors of the study are Tatsuyoshi Kawamura, Sandra S. Cohen, Debra L. Borris, Elisabeth A. Aquilino, Svetlana Glushakova, Leonid B. Margolis, Jan M. Orenstein, Robin E. Offord, A. Robert Neurath, and Andrew Blauvelt. The title of the study is "Candidate microbicides block HIV-1 infection of human immature Langerhans' cells within epithelial tissue explants." The Journal of Experimental Medicine, November 20, 2000, Volume 192, Number 10.