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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.

Original publication

DOI

10.1002/eji.200424889

Type

Journal article

Journal

Eur J Immunol

Publication Date

11/2004

Volume

34

Pages

3208 - 3215

Keywords

Amino Acid Sequence, CD8-Positive T-Lymphocytes, Cross Infection, DNA, Viral, Enzyme-Linked Immunosorbent Assay, HIV Infections, HIV-1, Hepatitis B, Hepatitis B Antibodies, Hepatitis B Surface Antigens, Hepatitis B virus, Humans, Interferon-gamma, Lymphocyte Activation, Oligopeptides, Peptide Fragments, Polymerase Chain Reaction, Sequence Analysis, DNA, Viremia