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The male lower urogenital tract is exposed to sexually transmitted pathogens and is therefore a strategic site of immune defense. To further define the immunodynamics of this region, we studied the histology, immune cell distribution, and draining lymph nodes of the murine male lower urogenital tract. The external surface of the foreskin was covered by skin composed of keratinized stratified epithelium containing numerous hair follicles and sebaceous glands. Immunologically the penile foreskin was characterized by the presence of few T lymphocytes and macrophages. Numerous Langerhans cells, however, were detected within the epithelium. The penile urethra was composed of stratified columnar epithelium, with a meatus lined by keratinized squamous epithelium preceding the opening proper. The most abundant immune cells of the penile urethra were macrophages. In young adult, virgin males, these were found primarily underlying the urethral epithelium, but in older, mated mice, they were usually intraepithelial in location, and were more abundant. Langerhans cells could not be specifically identified in the urethral mucosa. T lymphocytes were found underlying and occasionally within the epithelium of the urethral mucosa, with CD4+ cells more abundant than CD8+ cells. The majority of lymphocytes observed around the urethra were positive for the integrin beta 7 alpha M290, which is selectively expressed by mucosal lymphocytes, providing indirect evidence that the urethra is part of the common mucosal system. Lymphocytes expressing the gamma delta T cell receptor and IgA-positive plasma cells were not detected. The primary draining nodes for the vas deferens and urethra were the lumbar nodes. Lymphatic drainage from the rectum also involved the lumbar nodes. Information obtained in this study should help to elucidate optimal genital tract vaccination strategies for defense of the male urogenital tract against sexually transmitted pathogens.

Characterization of T Lymphocytes and Antigen-presenting Cells in the Murine Male Urethra