CD4⁺CD28null T lymphocytes resemble CD8⁺CD28null T lymphocytes in their responses to IL-15 and IL-21 in HIV-infected patients
| Autor: | José A. Carton, Ainara Echeverría, Rebeca Alonso-Arias, Carlos López-Larrea, Victor Asensi, Marco Antonio Moro-García |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Antigens Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes Male STAT3 Transcription Factor HIV Antigens Immunology chemical and pharmacologic phenomena HIV Infections Biology CD8-Positive T-Lymphocytes Cell Degranulation Granzymes Cohort Studies Interferon-gamma Young Adult Antigen CD28 Antigens Antigens CD STAT5 Transcription Factor Immunology and Allergy Humans Lectins C-Type Cell Proliferation Demography Interleukin-15 Perforin Interleukins Tumor Suppressor Proteins Null (mathematics) Degranulation CD28 hemic and immune systems Cell Biology T lymphocyte Middle Aged Up-Regulation Granzyme B biology.protein Female CD8 |
| Zdroj: | Journal of leukocyte biology. 98(3) |
| ISSN: | 1938-3673 |
| Popis: | HIV-infected individuals suffer from accelerated immunologic aging. One of the most prominent changes during T lymphocyte aging is the accumulation of CD28null T lymphocytes, mainly CD8+ but also CD4+ T lymphocytes. Enhancing the functional properties of these cells may be important because they provide antigen-specific defense against chronic infections. The objective of this study was to compare the responses of CD4+CD28null and CD8+CD28null T lymphocytes from HIV-infected patients to the immunomodulatory effects of cytokines IL-15 and IL-21. We quantified the frequencies of CD4+CD28null and CD8+CD28null T lymphocytes in peripheral blood from 110 consecutive, HIV-infected patients and 25 healthy controls. Patients showed increased frequencies of CD4+CD28null and CD8+CD28null. Both subsets were positively correlated to each other and showed an inverse correlation with the absolute counts of CD4+ T lymphocytes. Higher frequencies of HIV-specific and CMV-specific cells were found in CD28null than in CD28+ T lymphocytes. Activation of STAT5 by IL-15 and STAT3 by IL-21 was higher in CD28null compared with CD28+ T lymphocytes. Proliferation, expression of CD69, and IFN-γ production in CD28null T lymphocytes were increased after treatment with IL-15, and IL-21 potentiated most of those effects. Nevertheless, IL-21 alone reduced IFN-γ production in response to anti-CD3 stimulation but increased CD28 expression, even counteracting the inhibitory effect of IL-15. Intracytoplasmic stores of granzyme B and perforin were increased by IL-15, whereas IL-21 and simultaneous treatment with the 2 cytokines also significantly enhanced degranulation in CD4+CD28null and CD8+CD28null T lymphocytes. IL-15 and IL-21 could have a role in enhancing the effector response of CD28null T lymphocytes against their specific chronic antigens in HIV-infected patients. |
| Databáze: | OpenAIRE |
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