Evidence for intact costimulation via CD28 and CD27 molecules in hyporesponsive T cells from human immunodeficiency virus-infected individuals |
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Authors: | Linde Meyaard Heleen Kuiper Sigrid A Otto Katja C Wolthers Ren A W van Lier Frank Miedema |
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Institution: | Linde Meyaard,Heleen Kuiper,Sigrid A. Otto,Katja C. Wolthers,René A. W. van Lier,Frank Miedema |
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Abstract: | In the activation of T cells, the primary signal is antigen-specific and given through T cell receptor (TcR)/CD3 ligation. Furthermore, costimulatory molecules such as CD28 and CD27, provide an essential signal for activation through interaction with their ligands, present on the membrane of antigen-presenting cells. During asymptomatic human immunodeficiency virus (HIV)-1 infection, T cell function is progressively lost. Here, we investigated whether in the presence of impaired responses of T cells from HIV-infected individuals to signal one, costimulation through CD28 and CD27 after interaction with their natural ligands CD80 and CD70 is intact. T cell proliferative responses to signal one in combination with CD80 or CD70 were decreased in a large fraction of asymptomatically HIV-infected individuals. This was due to impaired responses of signal one but not to impaired responses to costimulation, since CD80 or CD70 did enhance signal one-mediated proliferative responses to a normal extent. Moreover, in individuals with proliferative responses to signal one that were decreased to 50% of normal T cell responses, costimulation even was increased compared to controls. Our results demonstrate that in HIV-infected individuals the response to costimulation is relatively preserved compared to responses to the first signal and point to the defect in T cells in HIV infection being primarily in the CD3/TcR-mediated pathway. |
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Keywords: | Human immunodeficiency virus infection CD27 CD70 CD28 CD80 |
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