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

Analysis of naïve lung CD4 T cells provides evidence of functional lung to lymph node migration

The proportion of CD4 T cells with phenotypic and functional properties of naïve cells out of total CD4 T cells is similar in the lung parenchyma and lymph nodes. On treatment with a sphingosine-1-phosphate agonist, the frequency of these cells falls precipitously, but with a delay of ∼14 h compared with blood CD4 T cells; neither anti-CD62L nor pertussis toxin prevents entry of naïve CD4 T cells into the lung. Based on treatment with anti-CD62L and the use of CCR7−/− cells, lung naïve CD4 T cells appear to migrate to the mediastinal lymph nodes along a CD62L-independent, CCR7-dependent pathway. Cells that have entered the node in this manner are competent to respond to antigen. Thus, a portion (approximately one-half) of naïve CD4 T cells appears to enter the mediastinal lymph nodes through a blood-to-lung-to-lymph node route

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-MHC class II antibody (Y3P) on the proliferation of MP cells. (A)

<p>2×10⁶ CD45.1 OT-II CD4 T cells were injected IP into CD45.2 FcγRγ^−/− B6 mice. 24 h later, mice were treated with Y3P (1.8 mg IP) or mouse immunoglobulin G (IgG), and 1 d later they were immunized IP with ovalbumin peptide (10 µg) plus LPS (25 µg) or LPS only. BrdU was given in drinking water from the time of immunization; 3 d later, lymph node cells were collected and stained with anti-CD45.1, anti-CD45.2, anti-CD44, anti-BrdU, and anti-Ki67. Contour plots were used because of the low number of cells available for analysis from mice treated with Y3P. (B) Numbers of CD45.1 and CD45.2 and of Ki-67⁺ BrdU⁺ cells from immunized control or Y3P-treated mice. (C) FcγRγ^−/− B6 mice were treated for 3 d with 1.8 mg of Y3P followed by a 6-h BrdU pulse (1 mg). Numbers in the quadrants represent the frequency of BrdU-positive and -negative and Ki-67-positive and -negative cells for an individual animal. Lower panels present means and SDs for numbers of BrdU⁺ and Ki-67⁺ cells among the three animals in each group.</p

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

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

Sequence diversity among proliferating and nonproliferating Vβ2-Jβ1.1 and Vβ4-Jβ1.1 CD44⁺, Foxp3⁻ cells CD4 T cells (1).

<p>Experimental approach to analyze the CDR3 sequences of Vβ2-Jβ1.1 and Vβ4-Jβ1.1 CD4⁺ CD44⁺ Foxp3⁻, KI-67^bright and Ki-67^negative cells from individual mice. Cells were FACS sorted into lysate buffer containing proteinase K. One-third of the lysate was subjected to PCR with specific Vβ and Jβ1.1 primers (see Methods). PCR products were cloned into the Topo vector followed by bacterial transformation and single colony isolation. PCR with universal M13 primers were used on each colony to amplify the Vβ2-Jβ1.1 and Vβ4-Jβ1.1 gene segments followed by sequencing with the universal T3 primer.</p