Regulatory T cells My research is focused on the development and function of T lymphocytes. In particular, I investigate the processes of thymic selection, immune tolerance and mechanisms of anti-tumor responses. The hallmark of the immune system is that T lymphocytes in healthy individuals recognize only “foreign” peptides and remain unresponsive to self-peptides/MHC complexes. Tolerance to self is enforced throughout T cell ontogeny, first in the thymus by physical elimination and later in peripheral organs by functional deletion of T cell clones expressing autoreactive TCRs. Recent years have brought the new paradigm that immune tolerance is established and maintained by active suppression mediated by the special subset of CD4+ T cells called regulatory T cells. Regulatory T cells do not have any specific molecules expressed on their surface to allow their discrimination form effector cells but they express transcription factor Foxp3+. These cells control normal immune system homeostasis and self-tolerance. In order to discriminate these cells we have produced transgenic mice expressing green fluorescent protein controlled by the Foxp3 regulatory sequences. These mice were used to isolate subsets of regulatory T cells and investigate their properties using cellular and functional assays. Recently we have found that the population of regulatory T cells in the peripheral lymphoid organs consists of two subsets that differ by the level of Foxp3 expression and functional characteristics. We have also analyzed global gene expression signature of regulatory T cells and various populations of effector T cells using GeneChip technologies. Information on the regulation of the gene expression may provide insight in to the mechanisms of immune suppression mediated by regulatory T cells. These cells are involved in inducing tolerance in cancer and are the major cause of failure of immunotherapy protocols in cancer.

Immune response in cancer The major impediment to investigate the ontogeny and functional status of antigen specific T cells is their low frequency in the population of naive T cells. To overcome this limitation I have generated mice expressing polyclonal but restricted TCR repertoire. Since the TCR repertoires in VJ/ chain transgenic mice are very narrow it is possible to follow what is the abundance of individual T cell clones in various T cells subsets including regulatory T cells. This mouse model is used to investigate immune response to conventional antigens and particularly immune response to tumor-associated antigens in cancer.

caBIONet--A .NET wrapper to access and process genomic data stored at the National Cancer Institute's Center for Bioinformatics databases.

Kraj P, McIndoe RA

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.

Presentation of antagonist peptides to naive CD4+ T cells abrogates spatial reorganization of class II MHC peptide complexes on the surface of dendritic cells.

Chmielowski B, Pacholczyk R, Kraj P, Kisielow P, Ignatowicz L

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta 30912, USA.

Peptide specificity of thymic selection of CD4+CD25+ T cells.

Pacholczyk R, Kraj P, Ignatowicz L

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.

Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset.

Kuczma, M., Podolsky, R., Garge, N., Daniely, D., Pacholczyk, R., Ignatowicz, L., and Kraj, P.

Journal of Immunology . 2009. in press

TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ Treg cells.

Kuczma, M., Pawlikowska, I., Kopij, M., Podolsky, R., Rempala, G. A., and Kraj, P.

Journal of Immunology . 2009. in press

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