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Immunological recovery failure in cART‐treated HIV‐positive patients is associated with reduced thymic output and RTE CD4+ T cell death by pyroptosis
Author(s) -
CarvalhoSilva Wlisses Henrique Veloso,
AndradeSantos José Leandro,
Souto Fabrício Oliveira,
Coelho Antonio Victor Campos,
Crovella Sergio,
Guimarães Rafael Lima
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.4a0919-235r
Subject(s) - pyroptosis , biology , cart , human immunodeficiency virus (hiv) , programmed cell death , immunology , cd4 t cell , t cell , immune system , virology , apoptosis , mechanical engineering , biochemistry , engineering
Despite more than three decades of studies and advances in combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV), the mechanisms that precisely determine immune reconstitution failure have not been completely elucidated yet. Thus, this study aimed to investigate the thymic function, immune activation, and cell death by pyroptosis and apoptosis in virologically suppressed HIV‐positive patients receiving cART. Immunophenotyping analyses were performed in 57 cART‐treated HIV‐infected patients with undetectable plasma viral load, who were classified as immunological nonresponders (INR = 29) and immunologic responders (IR = 28). Sociodemographic and clinical data were also assessed from medical records. Twelve healthy volunteers were also included in this study. The INR showed lower pretreatment CD4+ T cell count that remained low even after 1 yr of treatment, lower CD4/CD8 ratio, lower percentage of recent thymic emigrant (RTE) CD4+ T cell (CD45RA+CD31+) and naïve CD4+ T cell (CD45RA+CD62L+), higher levels of effector memory CD4+ T cells (CD45RA‐CD62L‐), and higher pyroptosis levels of RTE CD4+ T cells (CD31+FLICA‐Caspase1+) when compared with IR. Our findings indicate that reduced thymic function and RTE CD4+ T cell death by pyroptosis are the major mechanisms of immunological recovery failure in HIV‐infected patients receiving cART.