Haemophilus ducreyl causes chancroid, a common genital ulcer disease in developing countries, which facilitates HIV transmission. Lacking sufficient specimens from naturally infected patients, we developed an experimental model of the skin in human subjects. The predominant immune response during the first 2 weeks of experimental infection is a cellular infiltrate at the site of inoculation. There is a dermal infiltrate of mononuclear cells that are recruited within 24 hours of infection. The mononuclear cells are primarily T cells of the alphabeta lineage that express the memory marker, CD45RO. Sixty to 80% are CD4 cells, while the remainder are CD8 cells. HLA-DR expression on mononuclear and dendritic cells occurs within 24 hours of infection. The predominant cytokine mRNAs present throughout the infection are IFN-gamma, TNF- alpha and IL-8. The cutaneous immune responses in experimental and natural infection are similar and resemble a delayed typed hypersensitivity (DTH) responses. Recruitment of memory cells within 24 hours is intriguing since the subjects have no history of chancroid. For several infections, DTH responses contribute to immunopathology, and this application will focus on examining whether the T cell response to H. ducreyl antigens contributes to pathology. We hypothesize that epitopes shared by H. ducreyl and related gram-negative pathogens elicit an infiltrate of cross-reactive memory cells into the skin. Our second hypothesis is that a limited number of these cross reactive, immunodominant antigens elicit the stereotypic infiltrate of memory cells seen in all subjects who have been infected. Our third hypothesis is that the DTH response to the immunodominant antigens contributes to pathology. To test these hypotheses our aims include: Determination of proliferative responses of T cell lines isolated from experimental lesions to H. ducreyl and related species of the Pasteurellaceae that colonize the host; identification of specific H. ducreyl antigens that elicit the proliferative responses of the lines, and characterization of cytokine production of the lines in response to specific antigens; estimation of the precursor frequency and cytokine production of T cells directly isolated from lesions in response to the immmunodominant antigen(s) to cause a DTH response in humans.
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