High Eomesodermin Expression among CD57 + CD8 + T Cells Identifies a CD8 + T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection
| العنوان: | High Eomesodermin Expression among CD57 + CD8 + T Cells Identifies a CD8 + T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection |
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| المؤلفون: | Sandie Gérard, Alain Venet, Olivier Lambotte, Gianfranco Pancino, Asier Sáez-Cirión, Christine Bourgeois, Camille Lécuroux, Stephane Hua, Federico Simonetta, Faroudy Boufassa, Cécile Goujard |
| المصدر: | Journal of Virology. 88:11861-11871 |
| بيانات النشر: | American Society for Microbiology, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | 0303 health sciences, Receptor expression, T cell, Immunology, Eomesodermin, Biology, Microbiology, 3. Good health, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Immune system, medicine.anatomical_structure, Antigen, Virology, Insect Science, medicine, Cytotoxic T cell, CD8, 030304 developmental biology, 030215 immunology |
| الوصف: | During HIV infection, increased CD57 expression among CD8 + T cells has been associated with immune senescence and defective immune responses. Interestingly, CD57-expressing CD8 + T cells exhibit a dual profile, being simultaneously highly cytotoxic (terminally differentiated effectors) and poorly proliferative (replicative senescent). Recent publications point toward a positive role of CD57-expressing CD8 + T cell subsets, presumably due to their high cytolytic activity. We further investigated the phenotype of CD57-expressing CD8 + T cells in healthy donors and during HIV infection combining CD57 expression to Eomesodermin (EOMES), a T box transcription factor which determines, coordinately with T-bet, effector and memory CD8 + T cell differentiation. We defined in healthy donors two functionally distinct CD57-expressing CD8 + T cell subsets exhibiting different levels of EOMES expression: EOMES hi CD57 + and EOMES int CD57 + CD8 + T cells. EOMES hi CD57 + cells exhibited low cytotoxic activity but preserved proliferative capacity and interleukin 7 (IL-7) receptor expression, whereas EOMES int CD57 + cells exhibited obvious cytotoxic functions and a more terminally differentiated phenotype. We next performed a similar analysis in different contexts of HIV infection: primary infected patients, long-term viremic patients, aviremic patients treated with antiretroviral therapy, and HIV controllers; we demonstrated a higher percentage of CD57-expressing cells in all HIV-infected patients regardless of virological status. When heterogeneity in EOMES expression among CD57 cells was taken into account, we detected significantly higher proportions of EOMES hi CD57 + cells among HIV-specific and nonspecific CD8 + T cells from HIV controllers than in aviremic antiretroviral-treated patients and viremic patients. Importantly, such a peculiar non-terminally differentiated EOMES hi CD57 + phenotypic profile was associated with viral control. IMPORTANCE This study demonstrates that functional heterogeneity exists among CD57-expressing CD8 T cells, which include both terminally differentiated, highly cytotoxic EOMES int CD57 + CD8 + T cells and less differentiated EOMES hi CD57 + CD8 T cells, which do not exhibit immediate cytotoxic functions but present high proliferative capacity. Interestingly, HIV controllers present a high proportion of EOMES hi CD57 cells among CD57-expressing HIV-specific CD8 T cells compared to both long-term viremic and aviremic antiretroviral therapy (ART)-treated patients, suggesting a beneficial role for this cell subset in viral control. |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::f655421dcb96d7c9de6715f697d701f3Test https://doi.org/10.1128/jvi.02013-14Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........f655421dcb96d7c9de6715f697d701f3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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