Distinct phenotype of unrestricted cytotoxic T lymphocytes from human immunodeficiency virus-infected individuals.
BACKGROUND
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.


CONCLUSIONS
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.
Parsons
Matthew S
MS
Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Zipperlen
Katrin
K
Gallant
Maureen
M
Howley
Consie
C
Grant
Michael
M
D015703:Antigens, CD / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D055607:Receptors, Natural Killer Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D015703:Antigens, CD; D006680:HLA Antigens; D055607:Receptors, Natural Killer Cell