Distinct Phenotype of Unrestricted Cytotoxic T lymphocytes from Human Immunodeficiency Virus-infected Individuals
Matthew S. Parsons, Katrin Zipperlen, Maureen Gallant, Consie Howley, Michael Grant
Journal of Clinical Immunology
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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).
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.
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.
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.