Frequency of Vα24+Vβ11+ NKT cells in peripheral blood of human kidney transplantation recipients
Laboratory of Clinical and Experimental Immunology, Departamento de Medicina, Disciplina de Nefrologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil.International Immunopharmacology (Impact Factor: 2.47). 02/2005; 5(1):53-8. DOI: 10.1016/j.intimp.2004.09.013
There are still lacking data supporting a role for natural killer T (NKT) cells in the maintenance of human tissue-specific tolerance. We are interested to study NKT cell frequency in kidney transplant recipients and its correlation with graft function. Peripheral blood T cell receptors (TCR) Valpha24(+)Vbeta11(+) NKT cells were phenotyped according to CD4 and CD8 expression in normal controls (NC), in 10 years rejection-free cadaver kidney allografts maintained with minimal immunosuppression (long-term rejection free [LTRF]), in patients with acute rejection (AR) and in patients with acute tubular necrosis (ATN). Results were expressed as percentages of CD4(+)CD8(-) (CD4(+) NKT) or CD4(-)CD8(-) (double negative--DN NKT) Valpha24(+)Vbeta11(+) cells. The percentages of Valpha24(+)Vbeta11(+) cells were 0.09%, 0.14%, 0.02% and 0.09% on gated lymphocytes respectively in AR, ATN, LTRF and NC groups (p=0.263). DN NKT cells were more frequent in NC patients (52.11%) and less present in ATN patients (11.04%). In contrast, CD4(+) NKT (IL-4-producing NKT cells subset) was more frequent in AR (42.86%), and corresponded to almost 3 to 7 folds more what we obtained in the other groups. Although total Valpha24(+)Vbeta11(+) cells did not significantly differ among the groups, the lowest frequency was observed in the LTRF group. In conclusion, we observed that total number of NKT cells did not differ significantly among transplant patients when compared to normal controls, although specific-subsets seem to be more frequent in determined events.
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ABSTRACT: Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties characteristic of both T cells and NK cells and possess a variety of unusual properties with regard to antigen recognition and function. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids. The best known subset of CD1d-dependent NKT cells expresses an invariant T cell receptor a (TCR-a) chain. These are referred to as type I or invariant NKT cells (iNKT cells). These cells, which are the main focus of the current review, are conserved between humans and mice. Detailed work in mouse models has implicated iNKT cells in many immunological processes, and related studies in humans suggest important roles in health and disease. By virtue of their ability to produce a variety of immunoregulatory cytokines and to acquire a broad spectrum of effector activities, iNKT cells may both induce or suppress immune reactions in healthy and pathologic settings. We review the role of iNKT cells in the induction of tolerance to solid organ and hematologic transplants and malignancies, as well as their importance in maintaining normal self-tolerance and involvement in autoimmune diseases.
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ABSTRACT: SummaryA cross-regulation between two regulatory T cell (Treg) subsets [CD4+CD25+ and invariant natural killer (NK) T – iNK T] has been described to be important for allograft tolerance induction. However, few studies have evaluated these cellular subsets in stable recipients as correlates of favourable clinical outcome after heart transplantation. Treg and iNK T cell levels were assayed by flow cytometry in peripheral blood samples from 44 heart transplant recipients at a 2-year interval in 38 patients, and related to clinical outcome. Multi-parameter flow cytometry used CD4/CD25/CD127 labelling to best identify Treg, and a standard CD3/CD4/CD8/Vα24/Vβ11 labelling strategy to appreciate the proportions of iNK T cells. Both subtypes of potentially tolerogenic cells were found to be decreased in stable heart transplant recipients, with similar or further decreased levels after 2 years. Interestingly, the patient who presented with several rejection-suggesting incidents over this period displayed a greater than twofold increase of both cell subsets. These results suggest that CD4+CD25+CD127low/neg Treg and iNK T cells could be involved in the local control of organ rejection, by modulating immune responses in situ, in clinically stable patients. The measurement of these cell subsets in peripheral blood could be useful for non-invasive monitoring of heart transplant recipients, especially in the growing context of tolerance-induction trials.
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