Rabbit Anti-Human CD85k/LILRB4/ILT3 (a.a. 17-257) Polyclonal antibody

Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC subpopulations, including classical (cDCs) and plasmacytoid (pDCs) dendritic cells, are subjected to concomitant inflammatory and immunoregulatory events during HIV infection, which hampers the precise characterization of their regulation through classical approaches. Here, we carried out mass cytometry analysis of blood samples from early HIV-infected patients that were longitudinally collected before and after 1 year of effective combination antiretroviral therapy (cART). Blood samples from HIV controller patients who naturally control the infection were also included. Our data revealed that plasma HIV RNA level was positively associated with a loss of cDC and pDC subpopulations that display high expression of LILR immunomodulatory receptors. Conversely, specific monocyte populations co-expressing high levels of HLA-I, 3 immunomodulatory receptors, CD64, LILRA2, and LILRB4, and the restriction factor CD317 (also known as BST2/Tetherin), were more abundant in early HIV-infection. Finally, our analysis revealed that the blood of HIV controller patients contained in a higher abundance a particular subtype of CD1c(+) cDCs, characterized by elevated co-expression of CD32b inhibitory receptor and HLA-DR antigen-presentation molecules. Overall, this study unravels the modifications induced in DC and monocyte subpopulations in different HIV+ conditions, and provides a better comprehension of the immune regulation/dysregulation mechanisms induced during this viral infection.

The blockade of immune checkpoints by anti-receptor and/or anti-ligand mAb is one of the most promising approaches to cancer immunotherapy. The interaction between Ig-like transcript 3 (ILT3), a marker of tolerogenic dendritic cells, also known as LILRB4/LIR5/CD85k, and its still unidentified ligand on the surface of activated human T cells is potentially important for immune checkpoint blockade. To identify the ILT3 ligand, we generated mAb by immunizing mice with Jurkat acute T cell leukemia, which binds ILT3. Fc to its membrane. Flow cytometry, mass spectrometry, and Biacore studies demonstrated that the ILT3 ligand is a CD166/activated leukocyte cell adhesion molecule. Knockdown of CD166 in primary human T cells by nucleofection abolished the capacity of ILT3. Fc to inhibit CD4(+) Th cell proliferation and to induce the generation of CD8(+) CD28 2 T suppressor cells. CD166 displays strong heterophilic interaction with CD6 and weaker homophilic CD166-CD166 cell adhesion interaction. ILT3. Fc inhibited the growth of CD166(+) tumor cell lines (TCL) derived from lymphoid malignancies in vitro and in vivo. CRISPR-Cas9-based knockout of CD166 from TCL abrogated ILT3. Fc binding and its tumor-inhibitory effect. The mechanism underlying the effect of ILT3. Fc on tumor cell growth involves inhibition of the p70S6K signaling pathway. Blockade of CD166 by ILT3. Fc inhibited progression of human TCL in NOD. Cg-Prkdc Il-2rg/SzJ mice, suggesting its potential immunotherapeutic value.