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Biology subjects

Boss, A. P.

Publications and source records attributed to Boss, A. P..

2 recordsLinked to original sources

Differential composition of lymphocyte subpopulations and activation between the hypertensive Bph/2 and normotensive Bpn/3 mouse strains

Numerous studies point to a role for the immune system in various animal models of hypertension. However, little is known about the immune system of Bph/2 mice, a spontaneously hypertensive strain. To address this, we conducted a comprehensive comparison of immune cell composition and response to polyclonal T cell activation in hypertensive Bph/2 mice and normotensive Bpn/3 control mice. We quantified immune cell populations by flow cytometry from spleen and inguinal, brachial and mesenteric lymph nodes. While composition of myeloid immune cell types was largely comparable between strains, we observed differences in B and T cell subpopulations. Specifically, we found an increased percentage of IgM+ IgDLo and IgM+ IgD-B cells in Bph/2 mice, suggesting greater baseline B cell activation. In addition, we observed a decreased percentage of CD4 effector memory T cells and CD8 central memory T cells. The diminished proportion of memory T cells in Bph/2 mice correlated with decreased proliferation and cytokine response of splenic T cells to polyclonal T cell activation. In splenic T cells from Bph/2 mice 24 h after activation we observed a pronounced decrease in the majority of T cell cytokines. At 120 h after activation, the Th1 and Th17 cytokine responses of splenic T cells from Bph/2 mice were decreased, but other T cell cytokines were largely comparable. Overall, the data suggest a decreased percentage of memory T cells in Bph/2 mice that correlates with markedly diminished proliferation and a reduced cytokine response to polyclonal activation.

immunology↗

AML/T cell interactomics uncover correlates of patient outcomes and the key role of ICAM1 in T cell killing of AML

T cells are important for the control of acute myeloid leukemia (AML), a common and often deadly malignancy. We observed that some AML patient samples are resistant to killing by human engineered cytotoxic CD4+ T cells. Single-cell RNA-seq of primary AML samples and CD4+ T cells before and after their interaction uncovered transcriptional programs that correlate with AML sensitivity or resistance to CD4+ T cell killing. Resistance-associated AML programs were enriched in AML patients with poor survival, and killing-resistant AML cells did not engage T cells in vitro. Killing-sensitive AML potently activated T cells before being killed, and upregulated ICAM1, a key component of the immune synapse with T cells. Without ICAM1, killing-sensitive AML became resistant to killing to primary ex vivo-isolated CD8+ T cells in vitro, and engineered CD4+ T cells in vitro and in vivo. Thus, ICAM1 on AML acts as an immune trigger, allowing T cell killing, and could affect AML patient survival in vivo. SIGNIFICANCEAML is a common leukemia with sub-optimal outcomes. We show that AML transcriptional programs correlate with susceptibility to T cell killing. Killing resistance-associated AML programs are enriched in patients with poor survival. Killing-sensitive, but not resistant AML activate T cells and upregulate ICAM1 that binds to LFA-1 on T cells, allowing immune synapse formation which is critical for AML elimination. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/558911v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@84e2e1org.highwire.dtl.DTLVardef@4b2a40org.highwire.dtl.DTLVardef@c2d1f3org.highwire.dtl.DTLVardef@65db2c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗