INTRODUCTION: Human immunodeficiency virus (HIV)-infected individuals have CD8(+) cytotoxic T lymphocytes (CTL) that kill activated uninfected T lymphocytes. These CTL are independent of class Ia human histocompatibility-linked leukocyte antigens (HLA-Ia). METHODS: To further characterize these CTL, we investigated their possible restriction to non-classical class Ib HLA-E molecules and their expression of natural killer cell receptors (NKR) that are often affected in HIV infection. RESULTS: We found no role for HLA-E in CTL-mediated killing of activated uninfected T lymphocytes. The non-HLA-restricted CTL did not express NKG2A, an inhibitory NKR that binds HLA-E, nor CD56, a prominent marker on previously described non-HLA-restricted CTL. DISCUSSION: This NKG2A(-)CD56(-) phenotype of HLA-unrestricted CTL that kill uninfected activated T lymphocytes matches generalized changes on CD8(+) T lymphocytes that occur in progressive HIV infection, suggesting these phenotypic changes may reflect pathogenic evolution of the CD8(+) T cell repertoire. These CTL represent a unique phenotypic and functional subset with potential relevance to HIV pathogenesis.
INTRODUCTION:Human immunodeficiency virus (HIV)-infected individuals have CD8(+) cytotoxic T lymphocytes (CTL) that kill activated uninfected T lymphocytes. These CTL are independent of class Ia human histocompatibility-linked leukocyte antigens (HLA-Ia). METHODS: To further characterize these CTL, we investigated their possible restriction to non-classical class Ib HLA-E molecules and their expression of natural killer cell receptors (NKR) that are often affected in HIV infection. RESULTS: We found no role for HLA-E in CTL-mediated killing of activated uninfected T lymphocytes. The non-HLA-restricted CTL did not express NKG2A, an inhibitory NKR that binds HLA-E, nor CD56, a prominent marker on previously described non-HLA-restricted CTL. DISCUSSION: This NKG2A(-)CD56(-) phenotype of HLA-unrestricted CTL that kill uninfected activated T lymphocytes matches generalized changes on CD8(+) T lymphocytes that occur in progressive HIV infection, suggesting these phenotypic changes may reflect pathogenic evolution of the CD8(+) T cell repertoire. These CTL represent a unique phenotypic and functional subset with potential relevance to HIV pathogenesis.
Authors: V M Braud; D S Allan; C A O'Callaghan; K Söderström; A D'Andrea; G S Ogg; S Lazetic; N T Young; J I Bell; J H Phillips; L L Lanier; A J McMichael Journal: Nature Date: 1998-02-19 Impact factor: 49.962
Authors: J W Gratama; J W van Esser; C H Lamers; C Tournay; B Löwenberg; R L Bolhuis; J J Cornelissen Journal: Blood Date: 2001-09-01 Impact factor: 22.113