1984 B.S. - Department of Biochemistry and Molecular Biology, Wroclaw University, Poland.
1985 M.S - Department of. Biochemistry and Molecular Biology, Wroclaw University, Poland.
1990 PhD - Institute of Immunology and Experimental Therapy, Wroclaw, Poland.
Leszek Ignatowicz obtained his PhD from Institute of Immunology and Experimental Therapy in Wroclaw, Poland. In 2007 he was appointed a Professor of Immunology at Medical College of Georgia in Augusta University. His major research interests are: immune tolerance, T cells development and regulatory CD4+Foxp3+ T cells. Notable achievements include the characterization of TCR repertoire of thymus-derived regulatory T cells and their role in the maintenance of intestinal homeostasis.
Research in my laboratory is focused on studying the ontogeny and function of T lymphocytes using genetically manipulated mice. T lymphocytes express antigen receptors (also called T cell receptors-TCRs) that recognize antigens as short peptides bound to MHC. These peptides are derived from the body’s self-proteins or outside sources. In healthy individuals, T cells remain unresponsive (tolerant) to self-peptides/MHC complexes. Tolerance to self is enforced in the thymus, where developing thymocytes with high avidity TCRs against self MHC/peptide complexes are negatively selected. Normal thymocytes that survive selection express TCRs that very weakly recognize self-peptide/MHC complexes. An important feature of T cell development that remains to be explained is how self-peptide/MHC complexes can deliver both death-inducing signals that purge the repertoire of potentially harmful self-reactive T cells and positive signals that ensure survival but not overt activation. To determine how T lymphocytes with auto-aggressive specificities escape death in the thymus, we have studied mice that express MHC molecules bound exclusively with single, covalently attached peptide, instead of thousands of peptides that are naturally bound to MHC. The TCR repertoire in “single peptide” mice is not depleted of potentially autoreactive T cells that are found in peripheral lymphoid organs. Nevertheless, mice remain healthy because T cells selected in the thymus by one type of MHC/peptide complex are also only exposed to the same complexes in the rest of the body. However, when these mice receive cells from wild-type mice expressing the same MHC bound with many self-peptides, it elicits a robust T cells activation of T cells. These mice are therefore a valuable model to study how the lack of central tolerance provokes systemic and organ-specific autoimmunity.
During my research career, I have been studying the development and function of the immune system and mechanisms of organ specific autoimmune diseases, as evidenced by my recent publications. I also have a long standing interest in immunological tolerance, mucosal immune system, T cell development and bioinformatics applications related to the analysis of TCR diversity.
Our research demonstrated that when thymic selection occurs in the absence of multiple self-derived antigens bound to MHC, many T cells are activated by self-antigens and non-self, allo-antigens bound to MHC molecules. We also showed that subsets of CD4+ T cells that have effector or regulatory properties have comparable frequencies of clones that can recognize with high affinity self and non-self-antigens. Finally, we also presented evidence that intestinal homeostasis depends on thymus–derived regulatory T cells that induce tolerance to commensal-derived antigens. This research is important for our understanding how immune system develops and why immunoresponse to particular antigens can lead in some individuals an autoimmunity.
IN THE LAB:
We study different mechanisms of tolerance induction to self-antigens. In particular, we are interested in deciphering if thymus or peripherally derived regulatory T cells that express transcription factor Foxp3, have redundant or complimentary antigen specificities for self and non-self-antigens, respectively. For our work on the role of regulatory T cells in response to alloantigenes, in 2011 I received The Roche Organ Transplantation Research Foundation (ROTRF) Recognition Prize, that is awarded to investigators whose ROTRF-funded projects had a major impact on the field of transplantation.
- R. Pacholczyk, H. Ignatowicz, P. Kraj and L. Ignatowicz “Origin and TCR diversity of CD4+CD25+Foxp3+ T cells”. Immunity , 2006. 25, 249-259.
- R. Pacholczyk, J.Kern, N. Singh, M. Iwashima, P. Kraj and L. Ignatowicz “Non-self antigens are the cognate specificities of Foxp3+ TR cells.” Immunity, 2007, 27(3), 493-504
- M. Kuczma, R. Podolsky, N. Garge, D. Daniely, R. Pacholczyk, L. Ignatowicz, and P. Kraj ”Foxp3-Deficient Regulatory T Cells Do Not Revert into Conventional Effector CD4+ T Cells but Constitute a Unique Cell Subset” J. Immunol., 2009; 183: 3731 – 3741.
- D. Daniely, J. Kern, A. Cebula and L. Ignatowicz “Diversity of TCRs on natural Foxp3+ T cells in mice lacking Aire expression”. Diversity of TCRs on natural Foxp3+ T cells in mice lacking Aire expression” J. Immunol., 2010; 184: 6865 – 6873.
- N. Singh, R. Pacholczyk, M. Iwashima and L. Ignatowicz “Generation of T cell hybridomas from natural FoxP3+ regulatory T cells” Methods in Cell Biology, 2011. 707:39-44
- J. Van Valkenburgh, D.I. Albu, C. Bapanpally, S. Casanova, D. Califano, D. M. Jones,L. Ignatowicz, S. Kawamoto, S. Fagarasan,N. A. Jenkins, N. G. Copeland, P. Liu, D. Avram: “Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease” J. Exp. Med, 2011,208(10):2069-81.
- G.A. Rempala, Michal Seweryn, L. Ignatowicz “Model for Comparative Analysis of Antigen Receptor Repertoires” J. Theor. Biol., 2011, 269(1):1-15.G.A. Rempala, Michal Seweryn, L. Ignatowicz “Model for Comparative Analysis of Antigen Receptor Repertoires” J. Theor. Biol., 2011, 269(1):1-15.
- Sonne S, Shekhawat PS, Matern D, Ganapathy V, Ignatowicz L.:Carnitine deficiency in OCTN2-/- newborn mice leads to a severe gut and immune phenotype with widespread atrophy, apoptosis and a pro-inflammatory response. PLoS One. 2012;7(10):e47729. PMID: 23112839.
- Greene J, Birtwistle MR, Ignatowicz L, Rempala GA.: Bayesian multivariate Poisson abundance models for T-cell receptor data. J. Theor. Biol. 2013 Mar 1; 326C:1-10.
- Cebula A, Seweryn M, Rempala G.A, Pabla S.S, McIndoe R.A, Denning T.L, Bry L., Kraj P., Kisielow P., and Ignatowicz L: “Thymus-derived regulatory T cells control tolerance to commensal microbiota” Nature, 2013, 497(7448):258-62.
- Goto Y, Panea C, Lee C, Cebula A, Laufer T.M, Ignatowicz L, and Ivanov II “Presentation of segmented filamentous bacteria antigens by lamina propria dendritic cells drives mucosal Th17 cell differentiation” Immunity, 2014, 40(4),594–607.
- Wojciech L, Ignatowicz A, Seweryn M, Rempala G, Pabla S, McIndoe RA, Kisielow P and L. Ignatowicz “The same self-peptide selects conventional and regulatory T cells with identical antigen receptors.” Nature Comm., 2014, 5:5061. PMID: 25270305
- L. Wojciech and L. Ignatowicz “Tregs strip dendritic cells of CD70 to regulate Th1 differentiation” EMBO J. 2015, (34) 10,1290–1292.
- Kuczma M, C-Y Wang,L. Ignatowicz, R. Gourdie, P. Kraj “Altered Connexin 43 Expression Underlies Age-Dependent Decrease of Regulatory T Cell Suppressor Function in Nonobese Diabetic Mice” J. Immunol. 2015, 194, 5261-71.
- Szurek E, Cebula A, Wojciech L, Pietrzak M, Rempala G, Kisielow P, Ignatowicz L ”Differences in Expression Level of Helios and Neuropilin-1 Do Not Distinguish Thymus-Derived from Extrathymically-Induced CD4+Foxp3+ Regulatory T Cells. PLoS One. 2015 Oct 23;10(10):e0141161.