Journal Article

A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection

Wang, Yufei, Kaewkungwal, Jaranit, Yu, Xuesong, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Kim, Jerome H., Sato, Alicia, Lehner, Thomas, Britton, Gary, Michael, Nelson L., Robb, Merlin L., O’Connell, Robert J., Neil, Stuart, Rerks-Ngarm, Supachai, Whittall, Trevor, Mistry, Mukesh

2017

Overview

HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4 + T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated. In contrast, CD4 + TSCM cells expressing CCR5 co-receptors and α4β7 mucosal homing integrins were decreased. A parallel increase in CD4 + T cells was recorded with IL-15 receptors, APOBEC3G and CC chemokines, the latter downmodulating CCR5 molecules. We suggest a novel mechanism of dual memory stem cells; the established sequential memory pathway, TSCM →Central →Effector memory CD4 + T cells and the innate pathway consisting of the 4 subsets of TSCM. Both pathways are likely to be activated by endogenous HSP70. The TSCM memory stem cell and innate immunity pathways have to be optimised to boost the efficacy and immune memory of protection against HIV-1 in the clinical trial.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/100 / 13/106 / 13/21 / 13/31 / 631/250/255/1901 / 631/532/1360 / AIDS Vaccines - administration & dosage / AIDS Vaccines - immunology / Antiviral agents / CC chemokines / CCR5 protein / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / Clinical trials / Effector cells / HIV / HIV Infections - immunology / HIV Infections - prevention & control / HIV-1 - immunology / Hsp70 protein / Human immunodeficiency virus / Humanities and Social Sciences / Humans / Immunity, Innate / Immunologic Memory / Immunological memory / Innate immunity / Integrins / Interleukin 15 / Interleukin 15 receptors / Interleukin 2 / Lymphocytes / Lymphocytes T / Memory cells / Mucosa / multidisciplinary / Science / Science (multidisciplinary) / Stem cells / Stem Cells - physiology / Vaccines