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Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue "unhelped" CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells "help" the CD8 response during chronic infection via IL-21-induced BATF expression., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The CD1d-dependent presentation of lipid antigens to natural killer T (NKT) cells is an integral part of the innate immune system. However, the development of anticancer therapies based on NKT-cell agonists has had limited success so far. Humanizing mice with respect to the CD1d/NKT antigen presentation system will provide a tool to identify novel lipids that exert antineoplastic functions by targeting NKT cells before the initiation of costly and lengthy clinical trials.

Major histocompatibility complex (MHC) class I information is vital for understanding variance of immune responses in HIV vaccination and biomedical models. In this study, 9 Mamu-A and 13 Mamu-B alleles were identified from the cDNA products of 10 Chinese-origin rhesus macaques. Except for two alleles that had been reported by others, eight were novel and twelve extended the partial sequences that are available in GenBank. The additional information of MHC class I antigens might be beneficial to the availability of Chinese macaques in human disease studies. Furthermore, the polymorphism of leading peptides and the natural killer receptor recognition motifs in alpha1 domain both implies that Mamu-A and Mamu-B molecules might play key roles in innate immune responses of natural killer cells.