title: Influenza, but not HIV-specific CTL epitopes, elicits delayed-type hypersensitivity (DTH) reactions in HIV-infected patients.
abstract: The induction of cytotoxic T lymphocytes (CTLs) is believed to be an important defense mechanism against viral infections. The availability of simple, sensitive, specific and physiologically informative in vivo tests, applicable to humans, would greatly elucidate the nature of protective immune responses and facilitate immune monitoring in large vaccine trials. Here we studied the possibility of using defined HLA-A*02:01-restricted CTL epitopes from influenza matrix protein (GL9, GILGFVFTL) and HIV Gag p17 (SL9, SLYNTVATL) to elicit a cutaneous delayed-type hypersensitivity (DTH) reaction. Our results show that the GL9 but not the SL9 epitope was able to induce a DTH reaction. HIV infection status, HIV RNA level and CD4(+) T-cell counts were not predictive of the extent of DTH reactions. However, a markedly reduced expression of skin homing markers CD103 and cutaneous lymphocyte associated Ag (CLA) on epitope-specific CTL populations was associated with a lack of SL9 DTH reactivity. These data demonstrate that DTH reactions can be elicited by optimally defined CTL epitopes per se and point towards specific homing markers that are required for such reactions. These data may offer new insights into the immune pathogenesis of HIV infection and provide the basis of novel immune monitoring approaches for large-scale HIV vaccine trials.
authors.affiliation: IrsiCaixa AIDS Research Institute - HIVACAT, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Riol
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Victor
authors.initials: V
authors.lastname: Sanchez-Merino
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007114:Immunization; D007251:Influenza, Human / Q000276:immunology*; D009975:Orthomyxoviridae / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology / Q000378:metabolism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C473991:p17 gag peptide, human immunodeficiency virus