Evidence for extrathymic T cell maturation after thymectomy in infancy

Clinical and Experimental Immunology - Tập 145 Số 3 - Trang 407-412 - 2006
H Torfadottir1,2, Jona Freysdóttir3,2, I. Skaftadóttir4, Ásgeir Haraldsson5,1, Gunnlaugur Sigfússon5,1, Helga M. Ögmundsdóttir1
1Faculty of Medicine, University of Iceland, Reykjavik, Iceland
2Lyfjathroun hf-Biopharmaceuticals, Reykjavik, Iceland
3Centre for Rheumatology Research, Iceland
4Department of Immunology, Iceland
5Children‘s Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland

Tóm tắt

Summary Our previous study showed that children who had been partially or completely thymectomized during heart surgery as infants had lower proportions and numbers of total lymphocytes and reduced proportions of T cells (CD3+), helper T cells (CD4+) and naive T cells (CD3+ CD4+ CD45RA+), but normal proportion of cytotoxic T cells (CD8+). In this study T lymphocytes from a selected group of eight of these children and age- and gender-matched controls were characterized further using flow cytometry to determine phenotypes of T cells and T cell subsets related to T cell regulation and phenotypes suggestive of extrathymic maturation. Immune function was assessed by measuring autoantibodies and antibodies against vaccines. The study group had significantly lower numbers of all the main subsets of T lymphocytes and the composition was different. Thus, the proportions of lymphocytes with the following phenotypes: CD3+, CD2+, CD7+, CD4+, CD62L+, CD4+ CD62L+ and CD4+ CD69– were significantly reduced in the study group compared with the control group, but significantly higher proportions were seen of lymphocytes expressing CD8α+ CD8β– and TCRγδ+ CD8α+ CD8β–. The absolute number and proportion of CD4+ CD25+ cells were reduced but the proportions of the subgroup of naive regulatory T cells (CD4+ CD25+ CD62L+) and non-activated regulatory T cells (CD4+ CD25+ CD69–) were not reduced in the thymectomized children. We conclude that the phenotypic characteristics of T lymphocytes of children who have lost their thymus in infancy are indicative of extrathymic maturation. T regulatory cells appear to be less affected than other subsets by the general reduction in T cell numbers.

Từ khóa


Tài liệu tham khảo

Janeway, 2001, Immunobiology: the immune system in health and disease, 5th edn

Petrie, 1990, Lineage relationships and developmental kinetics of immature thymocytes. CD3, CD4, and CD8 acquisition in vivo and in vitro, J Exp Med, 172, 1583, 10.1084/jem.172.6.1583

Umetsu, 2003, Regulatory T cells control the development of allergic disease and asthma, J Allergy Clin Immunol, 112, 480, 10.1016/S0091-6749(03)01869-4

Nakamura, 2003, CD4+ NKT cells, but not conventional CD4+ T cells, are required to generate efferent CD8+ T regulatory cells following antigen inoculation in an immune-privileged site, J Immunol, 171, 1266, 10.4049/jimmunol.171.3.1266

Cortesini, 2001, CD8+CD28– T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity, Immunol Rev, 182, 201, 10.1034/j.1600-065X.2001.1820116.x

Abo, 2001, Extrathymic pathways of T cell differentiation and immunomodulation, Int Immunopharmacol, 1, 1261, 10.1016/S1567-5769(01)00057-1

Blais, 2003, Extrathymic T-lymphocyte development, Exp Hematol, 31, 349, 10.1016/S0301-472X(03)00026-2

Nonaka, 2005, Intestinal gamma delta T cells develop in mice lacking thymus, all lymph nodes, Peyer’s patches, and isolated lymphoid follicles, J Immunol, 174, 1906, 10.4049/jimmunol.174.4.1906

Suzuki, 2000, Gut cryptopatches: direct evidence of extrathymic anatomical sites for intestinal T lymphocytes, Immunity, 31, 691, 10.1016/S1074-7613(00)00068-6

Sato, 1995, Evidence for extrathymic generation of intermediate T cell receptor cells in the liver revealed in thymectomized, irradiated mice subjected to bone marrow transplantation, J Exp Med, 182, 759, 10.1084/jem.182.3.759

Camarero, 2000, Intraepithelial lymphocytes and coeliac disease. permanent changes in CD3–/CD7+ and T cell receptor γδ subsets studied by flow cytometry, Acta Paediatr, 89, 285

Eiras, 2000, Intestinal intraepithelial lymphocytes contain a CD3– CD7+ subset expressing natural killer markers and a singular pattern of adhesion molecules, Scand J Immunol, 52, 1, 10.1046/j.1365-3083.2000.00761.x

Eysteinsdottir, 2004, The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life, Clin Exp Immunol, 136, 349, 10.1111/j.1365-2249.2004.02437.x

Brearley, 1987, Immunodeficiency following neonatal thymectomy in man, Clin Exp Immunol, 70, 322

Wells, 1998, Neonatal thymectomy: does it affect immune function?, J Thorac Cardiovasc Surg, 115, 1041, 10.1016/S0022-5223(98)70403-9

Halnon, 2005, Thymic function and impaired maintenance of peripheral T cell populations in children with congenital heart disease and surgical thymectomy, Pediatr Res, 57, 42, 10.1203/01.PDR.0000147735.19342.DE

Guy-Grand, 2003, Extrathymic T cell lymphopoiesis; ontogeny and contribution to gut intraepithelial lymphocytes in athymic and euthymic mice, J Exp Med, 197, 333, 10.1084/jem.20021639

Wang, 2001, Phenotypic comparison of extrathymic human bone-marrow-derived T cells with thymic-selected T cells recovered from different tissues, Clin Immunol, 100, 339, 10.1006/clim.2001.5068

Fry, 2001, Interleukin-7: master regulator of peripheral T cell homeostasis, Trends Immunol, 22, 564, 10.1016/S1471-4906(01)02028-2

Mackall, 1997, Restoration of T cell homeostasis after T cell depletion, Semin Immunol, 9, 339, 10.1006/smim.1997.0091

Hazenberg, 2003, Thymic output: a bad TREC record, Nat Immunol, 4, 97, 10.1038/ni0203-97

McFarland, 2000, Identification of a human recent thymic emigrant phenotype, Proc Natl Acad Sci USA, 97, 4215, 10.1073/pnas.070061597

Agace, 2000, T-lymphocyte–epithelial–cell interactions: integrin αE (CD103) β7, LEEP-CAM and chemokines, Curr Opin Biol, 12, 563, 10.1016/S0955-0674(00)00132-0