- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
- vaccines and immunoinformatics approaches
- Hematopoietic Stem Cell Transplantation
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Virus-based gene therapy research
- Immune Response and Inflammation
- Childhood Cancer Survivors' Quality of Life
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- Autoimmune and Inflammatory Disorders Research
- RNA Interference and Gene Delivery
- Neonatal Respiratory Health Research
- Mast cells and histamine
- Renal Transplantation Outcomes and Treatments
- Pancreatic function and diabetes
- Cytomegalovirus and herpesvirus research
- Asthma and respiratory diseases
- Reproductive System and Pregnancy
University of Mons
2025
Institut Jules Bordet
2025
Université Libre de Bruxelles
2025
Memorial Sloan Kettering Cancer Center
2004-2024
Rutgers, The State University of New Jersey
2013-2023
Johnson University
2012-2023
Rutgers Sexual and Reproductive Health and Rights
2016-2023
Rutgers Cancer Institute of New Jersey
2019-2023
Graduate School USA
2023
Medizinische Hochschule Hannover
2013
Significance Immunotherapy has revolutionized cancer treatment, yielding unprecedented long-term responses and survival. However, a significant proportion of patients remain refractory, which correlates with the absence immune-infiltrated (“hot”) tumors. Here, we observed that FDA-approved unadjuvanted seasonal influenza vaccines administered via intratumoral injection not only provide protection against active virus lung infection, but also reduce tumor growth by increasing antitumor CD8 +...
HLA-DM is a major histocompatibility complex (MHC) class II–like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain–derived peptides (CLIP) from II molecules for antigenic peptides. HLA-DO second physically associates with in B cells. was shown to block function. Purified HLA-DM-DO complexes could not promote peptide vitro. Expression + and DM , DO − human T cell line caused accumulation II–CLIP complexes, indicating blocked function vivo suggesting an...
Despite our knowledge of the protective role antibodies passed to infants through breast milk, understanding immunity transfer via maternal leukocytes is still limited. To emulate immunological interface between mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched MHC-mismatched dams. Overall, data revealed that: 1) Survival milk in suckling possible, but not significant foster-nursing ceases; 2) Most lymphocytes establish themselves specific...
Abstract The broad-complex tramtrack and bric a brac-zinc finger transcriptional regulator(BTB-ZF), promyelocytic leukemia zinc (PLZF), was recently shown to control the development of characteristic innate T cell phenotype effector functions NK cells. Interestingly, ectopic expression PLZF push conventional cells into an activated state that seems be proinflammatory. factors normal in lymphocytes are unknown. In this study, we show is not restricted but also expressed by subset γδ cells,...
A T cell–mediated immune response is mainly determined by the 3–5 aa residues that protrude upwards from a peptide bound to an MHC molecule. Alterations of these can diminish, eliminate or radically alter signal cell receives through its receptor (TCR). We have used immunizations normal mice and carrying α β chain TCR transgenes identify three distinct contact points. One, near carboxyl terminus peptide, involves CDR3 region; second was centrally located interacted with both loops; third...
Seventy percent of peripheral immature conventional (B2) B cells fail to develop into mature cells. The nature this cell loss has not been characterized; the process that governs which long-lived could be either stochastic or selective. Here, we demonstrate step is in fact selective, fate an highly dependent on its Ig receptor specificity. A significant skewing repertoire occurs by time enter fraction, indicates there selection only a minority become Because few heavy-light chain pairs are...
Abstract Priming of naive CD4+ T cells to Ag requires an antigen-presenting cell (APC) that can take up the and present peptide bound MHC class II molecules. We have used both in vivo vitro approaches demonstrate APC prime depends on initial form which is administered. Although delivered as a was presented most efficiently by DC, these were poor at priming protein same Ag. In contrast, presence B requisite for
Summary: Invariant natural killer T (iNKT) cells comprise a rare lymphocyte sublineage with phenotypic and functional properties similar to NK cells. Akin conventional αβ cells, their development occurs primarily in the thymus, where they originate from CD4 + CD8 double positive (DP) progenitors. However, selection of iNKT is unique that it mediated by homotypic interactions DP recognition glycolipid antigen‐CD1d complexes. Additionally, acquire an activated innate‐like phenotype during...
The broad complex, tramtrack, bric-a-brac-zinc finger (BTB-ZF) transcription factor promyelocytic leukemia zinc (PLZF) is required for development of the characteristic innate/effector functions NKT cells. In this study, we report characterization and functional analysis transgenic mouse T cells with forced expression PLZF. PLZF was sufficient to provide some memory/effector without need Ag stimulation or proliferation. acquisition phenotype did not require proliferation typically associated...
Abstract Successful immunity depends upon the activity of multiple cell types. Commitment pluripotent precursor cells to specific lineages, such as T or B cells, is obviously fundamental this process. However, it also becoming clear that continued differentiation and specialization lymphoid equally important for immune system integrity. Several members BTB-ZF family have emerged critical factors control development lineages effector subsets within these lineages. For example, genes been...
The analysis of T cell receptor alpha (TCR alpha) chains in mice transgenic for a TCR beta chain has allowed us to demonstrate central role self-peptides the positive intrathymic selection major histocompatibility complex (MHC) class II-restricted cells. Analysis specific V alpha-J joins mature CD4+ TCRhigh thymocytes and peripheral cells revealed limitation amino-acid sequences. By immature thymocytes, we could show that this limited repertoire was selected from more diverse repertoire....
Peptide loading of MHC class II (MHCII) molecules is directly catalyzed by the MHCII-like molecule HLA-DM (DM). Another molecule, HLA-DO (DO), associates with DM, thereby modulating DM function. The biological role DO-mediated regulation activity in vivo remains unknown; however, it has been postulated that DO expression dampens presentation self antigens, preventing inappropriate T cell activation ultimately leads to autoimmunity. To test idea modulation MHCII self-peptide repertoire...
Conventional and nonconventional T cell development occur in the thymus. Nonconventional thymocytes that bear characteristics typically associated with innate immune cells are termed innate-like lymphocytes (ILLs). Mice harboring a tyrosine to phenylalanine mutation adaptor protein Src homology 2 domain-containing leukocyte of 76 kDa at residue 145 (Y145F mice) develop an expanded population CD8(+)CD122(+)CD44(+) ILLs, typified by expression T-box transcription factor eomesodermin. Y145F...
Unlike conventional αβT cells, invariant natural killer T (iNKT) cells complete their terminal differentiation to functional iNKT1/2/17 in the thymus. However, underlying molecular programs that guide iNKT subset remain unclear. Here, we profiled transcriptomes of over 17,000 and chromatin accessibility states 39,000 across four thymic developmental stages using single-cell RNA sequencing (scRNA-seq) assay for transposase-accessible (scATAC-seq) define trajectories. Our study discovered...
Using a sensitive molecular marker for positive selection, the appearance of particular functional TCR α chain sequence in cells from mice bearing transgenic β chain, we address several aspects intrathymic T cell development. First, by examining specific prior to and after maturation, demonstrate how restricted repertoire is positively selected highly diverse immature repertoire. Second, since this enriched progressing toward CD4 lineage depleted CD8 lineage, map developmental pathway αβ...
In mice, the transcription factor, PLZF, controls development of effector functions in invariant NKT cells and a subset cell-like, γδ T cells. Here, we show that human lymphocytes, addition to cells, PLZF was also expressed large percentage CD8+ CD4+ Furthermore, found be all NK Importantly, donor lacking functional these various lymphocyte populations were altered. Therefore, contrast appears control and/or function wide variety lymphocytes represent more than 10% total PBMCs....
Invariant natural killer T cells have a distinct developmental pathway from conventional αβ cells. Here we demonstrate that the transcriptional repressor NKAP is required for invariant cell but not development. In CD4-cre conditional knockout mice, development blocked at double-positive stage. This cell-intrinsic block due to decreased survival or failure rearrange Vα14-Jα18 receptor-α chain, rescued by overexpression of rec-Vα14-Jα18 transgene stage, thus defining role in selection into...