Dysfunctional phenotypes of CD4+ and CD8+ T cells are comparable in patients initiating ART during early or chronic HIV-1 infection
| Autor: | Bo Hejdeman, Sylvie Amu, Francesca Chiodi, Aikaterini Nasi, Rebecka Lantto Graham, Genny Meini, Sam Sorial, Maurizio Zazzi, Carina Bengtsson, Bence Rethi, Yonas Bekele |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Observational Study Activation Human leukocyte antigen CD38 Differentiation Early ART HIV-1 Immunoactivation Inflammation markers T-cell phenotype Virus reservoirs Medicine (all) 03 medical and health sciences 0302 clinical medicine Antigen Medicine Cytotoxic T cell 030212 general & internal medicine Interleukin-7 receptor business.industry Beta-2 microglobulin CD28 General Medicine 030104 developmental biology Immunology ComputingMethodologies_DOCUMENTANDTEXTPROCESSING business CD8 Research Article |
| Zdroj: | Medicine |
| Popis: | Supplemental Digital Content is available in the text Early initiation of antiretroviral therapy (ART) is becoming a common clinical practice according to current guidelines recommending treatment to all HIV-1-infected patients. However, it is not known whether ART initiated during the early phase of infection prevents the establishment of abnormal phenotypic features previously reported in CD4+ and CD8+T cells during chronic HIV-1 infection. In this cross-sectional study, blood specimens were obtained from 17 HIV-1-infected patients who began ART treatment shortly after infection (early ART [EA]), 17 age-matched HIV-1-infected patients who started ART during chronic phase of infection (late ART [LA]), and 25 age-matched non-HIV-1-infected controls. At collection of specimens, patients in EA and LA groups had received ART for comparable periods of time. Total HIV-1 DNA was measured in white blood cells by quantitative PCR. The concentration of 9 inflammatory parameters and 1 marker of fibrosis, including sCD14 and β-2 microglobulin, was measured in plasma. Furthermore, expression of markers of abnormal immune activation (human leukocyte antigen - antigen D related [HLA-DR] and CD38), exhaustion (programmed death 1, CD28, CD57) and terminal differentiation (CD127) was measured on CD4+ and CD8+T cells. T-cell proliferation was measured through Ki67 expression. The copies of total HIV-1 DNA in blood were significantly lower (P = 0.009) in EA compared with that in LA group. Only the expression of HLA-DR on naïve CD4+ T cells distinguished EA from LA, whereas expression of 3 surface markers distinguished T-cell populations of HIV-1-infected patients from controls. These included HLA-DR distinguishing CD4+ T cells from EA compared with controls, and also CD38 and CD127 on CD4+ and CD8+ T cells, respectively, distinguishing both groups of patients from controls. The sCD14 levels were significantly higher in EA patients, and β-2 microglobulin levels were higher in LA group compared with that in controls. Our results demonstrate an equivalent abnormal expression of activation (HLA-DR and CD38 on CD4+ T cells) and terminal differentiation (CD127 on CD8+ T cells) markers in T cells from both EA and LA patients. The size of total HIV-1 DNA copies in blood of EA was lower compared with LA patients. These findings suggest that some abnormalities taking place in the T-cell compartment during primary HIV-1 infection may not be corrected by early ART. |
| Databáze: | OpenAIRE |
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