Parenteral exposure to high HIV viremia leads to virus-specific T cell priming without evidence of infection |
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Authors: | Missale Gabriele Papagno Laura Penna Amalia Pilli Massimo Zerbini Alessandro Vitali Piero Pieroni Giovanni Urbani Simona Uggeri Jacopo Pinheiro Susana Rowland-Jones Sarah Ferrari Carlo |
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Institution: | Laboratorio di Immunopatologia Virale, Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. missale@tin.it |
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Abstract: | Previous studies on CTL responses in HIV-exposed uninfected individuals assumed that the patients were exposed to replicating HIV, but the possibility that the immune responses detected were primed by exposure to a defective virus or viral antigen could not be excluded. Epidemiological and laboratory analysis of a nosocomial outbreak of acute hepatitis B unequivocally allowed the identification of an HIV-1- and HBV-co-infected patient with high plasma levels of both viruses, as the source case of the epidemics. This clinical setting provided a natural model for testing the HIV-specific T cell response in patients exposed to blood from a patient with highly replicating HIV. Parenteral exposure to both viruses led to acute hepatitis B in five subjects without evidence of HIV-1 infection. Cryopreserved lymphocytes derived from three exposed patients were tested ex vivo in an ELISPOT assay for IFN-gamma release upon stimulation with peptides from structural and non-structural HIV proteins; one of the patients was also tested with four HLA/class I tetramers. Circulating HIV-specific CD8 cells were detected by tetramer staining and a high frequency of T cells were able to release IFN-gamma upon stimulation with HIV peptides, showing in vivo T cell priming by HIV. These results unequivocally demonstrate a HIV-specific cell-mediated immune response in the absence of infection after exposure to highly replicating HIV. |
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Keywords: | HIV HBV T cell response |
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