T-Subset Abnormalities in Thalassaemia intermedia: Possible Evidence for a Thymus Functional Deficiency

Abstract

Peripheral blood T-lymphocyte subsets, evaluated by means of a series of monoclonal antibodies, were assessed in 14 patients affected by thalassaemia intermedia, 7 of them previously splenectomized. A significant reduction of T⁺₄ cells (‘helper’ T cells) was found in almost all patients, whereas T⁺₈ cells (‘suppressor/cytotoxic’) showed a marked increase only in splenectomized subjects. Together with these quantitative T-subset abnormalities, which seemed to be partly affected by either splenectomy or high serum iron levels, an unusual circulating T-cell subpopulation labelled by T₆ monoclonal antibody was detected in all patients. Complete disappearance of T- cells (‘thymo-cyte-like’ T lymphocytes) and normalization of the T₄/T₈ ratio was observed after ‘in vitro’ incubation of patient’s lymphocytes with a crude thymus extract (Thymostimulin). This would suggest the presence of a so far unreported thymus-dependent defect of T-lymphocyte phenotypic maturation occurring in thalassaemia intermedia.

Immunological Evaluation of Patients with Beta-Thalassemia major

“…They include: impaired activity of monocytes and neutrophils [4, 5], defective activity of the complement alternative pathway [6], increased polyclonal serum immunoglobulin levels [1, 2, 3], numerical or functional alterations of different peripheral blood lymphocyte subpopulations [1, 2, 3, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]and anomalies of serum levels of cytokines and soluble antigens [3]. The pathogenic mechanism of these abnormalities is not clarified.…”

“…The pathogenic mechanism of these abnormalities is not clarified. Factors such as splenectomy [7, 8, 16, 19], iron overload [7, 8, 16, 19, 20], repeated exposure to foreign antigens at the time of blood transfusions [19, 21, 22]and the use of the chelating agent deferoxamine (DFO), known to have profound effects on the immune system, have been considered [12, 23]. The role of immunologic alterations on the clinical course of TM is not established, although they have been considered relevant to infectious episodes that these patients suffer [8].…”

A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with β-thalassaemia

“…Transfusions lead to iron overload and also to immune derangements, both of which exert a negative effect on the functional integrity of the immune system in multitransfused patients with thalassaemia. There are already a large number of reports describing immune abnormalities in thalassaemia, namely defective function of polymorphonuclear neutrophils and monocytes [2,3], decrease of CD4 + cells and increase of CD8 + cells [4][5][6], diminished mitogen responses [5] and low natural killer (NK) cell activity [7,8]. These and probably other undetected abnormalities may explain the tendency for severe or unusual infections.…”

Lack of Plasma Protein Hemopexin Dampens Mercury-Induced Autoimmune Response in Mice

“…In contrast, rats loaded with iron have been reported to have an increase in CD8 ϩ cells. However, the relationship between iron overload and the immune response is controversial, as other studies have shown that transfusional iron overload in thalassemia intermedia patients is associated with a blunted response of T cells to mitogens and with decreases in circulating CD4 ϩ cells and CD4/CD8 ratios (4). Finally, on investigating the effect of iron status on murine systemic lupus erythematosus, Leiter et al have found that iron supplementation leads to more severe renal disease and increases mortality (5).…”

“…It binds free heme and mediates its uptake in liver cells through receptor-mediated endocytosis. Heme is then catabolized by heme oxygenase (HO) 4 into biliverdin, carbon monoxide (CO), and iron. In this way, hemopexin is thought to prevent heme-iron loss and the proinflammatory effects of free heme.…”