Parenteral exposure to high HIV viremia leads to virus-specific T cell priming without evidence of infection.
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.
Missale
Gabriele
G
Laboratorio di Immunopatologia Virale, Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. missale@tin.it
Papagno
Laura
L
Penna
Amalia
A
Pilli
Massimo
M
Zerbini
Alessandro
A
Vitali
Piero
P
Pieroni
Giovanni
G
Urbani
Simona
S
Uggeri
Jacopo
J
Pinheiro
Susana
S
Rowland-Jones
Sarah
S
Ferrari
Carlo
C
D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003428:Cross Infection / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006509:Hepatitis B / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014766:Viremia / Q000276:immunology / Q000821:virology
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D009842:Oligopeptides; D010446:Peptide Fragments; D007371:Interferon-gamma