Reconstitution of CD4+ T cell responses in HIV-1 infected individuals initiating highly active antiretroviral therapy (HAART) is associated with renewed interleukin-2 production and responsiveness |
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| Authors: | Hardy G A D Imami N Sullivan A K Pires A Burton C T Nelson M R Gazzard B G Gotch F M |
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| Affiliation: | Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, London. g.hardy@imperial.ac.uk |
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| Abstract: | Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy. |
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| Keywords: | interleukin‐2 interleukin‐4 highly active antiretroviral therapy (HAART) lymphocyte proliferation T cell anergy |
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