New cutaneous vaccine adjuvant that STINGs a little less

Cutaneous vaccination can be a challenge because the development of local skin inflammation is often unavoidable. Thus, it is important to identify and validate new vaccine adjuvants that enhance immunization without the burden of inflammation. Wang et al. now report on a cyclic GMP-AMP adjuvant, the natural stimulator of interferon genes agonist, providing evidence for potent immune responses without inflammation

IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells

Here, we show that interleukin-1 (IL-1) enhances antigen-driven CD8 T cell responses. When administered to recipients of OT-I T cell receptor transgenic CD8 T cells specific for an ovalbumin (OVA) peptide, IL-1 results in an increase in the numbers of wild-type but not IL1R1−/− OT-I cells, particularly in spleen, liver, and lung, upon immunization with OVA and lipopolysaccharide. IL-1 administration also results in an enhancement in the frequency of antigen-specific cells that are granzyme B+, have cytotoxic activity, and/ or produce interferon γ (IFN-γ). Cells primed in the presence of IL-1 display enhanced expression of granzyme B and increased capacity to produce IFN-γ when rechallenged 2 mo after priming. In three in vivo models, IL-1 enhances the protective value of weak immunogens. Thus, IL-1 has a marked enhancing effect on antigen-specific CD8 T cell expansion, differentiation, migration to the periphery, and memory

Memory Phenotype CD4 T Cells Undergoing Rapid, Nonburst-Like, Cytokine-Driven Proliferation Can Be Distinguished from Antigen-Experienced Memory Cells

Contrary to the current paradigm that nearly all memory T cells proliferate in response to antigenic stimulation, this paper shows that an important population of CD4 T lymphocytes achieves memory/effector status independent of antigenic stimulation

At the innate frontiers between mother and fetus: linking abortion with complement activation

The intricate mechanisms regulating fetomaternal interactions are still largely uncharacterized. Recent papers have revealed a major role for the innate immune system during abortion. Different experimental conditions—deletion of a complement regulator, injection of anti-phospholipid antibodies into mothers, or allorecognition of fetuses in the presence of an IDO inhibitor—all lead to complement activation, inflammation, and fetal loss. These observations also raise new questions on the relationship between the adaptive and innate systems during pregnancy

Effect of anti–IL-7Rα, anti–IL-15, and anti–IL-2 on in situ MP proliferation.

<p>Normal B6 mice were either untreated or received two doses of 0.5 mg of anti–IL-15, anti–IL-7Rα, or anti–IL-2 antibody spaced 3 d apart. Mice were humanely killed on day 7 and lymph node cell suspensions were stained with anti-CD4, anti-CD44, and anti–Ki-67. *<i>p</i><0.05.</p

Sequence diversity among proliferating and nonproliferating Vβ2-Jβ1.1 cells in B6 GF mice.

<p>Sequence diversity among Ki-67^bright and Ki-67^negative Vβ2-Jβ1 CD44⁺ CD4 T-cell populations. Shown is the percentage of times an individual sequence occurred in two GF mice.</p

Effect of anti–IL-7, anti–IL-15, and anti-MHC class II (CII) on MP proliferation in Rag 2−/− mice.

<p>(A) 1 million CFSE-labeled MP CD4 T cells were transferred into Rag 2−/− mice that received a single dose of 0.5 mg of anti–IL-7, anti–IL-15, or 1.8 mg of Y3P or were untreated. On day 3, the mice received a second dose of anticytokine antibody or of Y3P. Mice were humanely killed on day 6 and single cell suspensions from lymph nodes were stained by anti-CD4 followed by flow cytometric analysis of CFSE dilution. Numbers inside the histograms represent the frequency of cells that have divided at least once (mean ± SD, from three mice per group). (B) 1 million CFSE-labeled MP CD4 T cells were transferred into Rag2−/− recipients. On day 3, animals were humanely killed and 50×10³ CFSE low and high cells were sorted, followed by PCR amplification using Vβ2 and Jβ1.1 primers (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001171#pbio-1001171-g006" target="_blank">Figure 6A</a>). CDR3 sequences from the amplified DNA were plotted according to the frequency with which they appeared among the 42 sequences obtained from CFSE low and high Vβ2/Jβ1.1 cells, respectively.</p