Treatment of T cell proliferation with monoclonal antibody.
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Biomedical subjects
Publications and source records attributed to D C Linch.
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Morphological, surface-marker and culture studies were performed in three patients who had in common neutropenia and an excess of lymphocytes in the bone marrow, but who differed from each other in certain regards such as age and peripheral lymphocyte numbers. All three patients had an increased proportion of E-rosetting cells bearing Fc receptors for IgG. These cells were shown to be T lymphocytes by staining with monoclonal anti-T-cell sera and their subset phenotype was established as OKT4- OKT8+; in addition, a variable proportion of the cells was Ia+. The functional significance of this expanded subpopulation of T cells was not clear, but it was shown that they did not inhibit colony formation in vitro.
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A case of steroid-resistant acquired pure red-cell aplasia associated with a relative and absolute increase of TG cells is described. Removal of T cells enhanced erythroid colony and burst formation in vitro, and it is suggested that TG cells may be implicated in the pathogenesis of this case of acquired pure red-cell aplasia.
Rapid progression of aortic regurgitation was closely observed in a patient with severe seropositive rheumatoid arthritis. Rheumatoid changes within the aortic valve leaflets resulted in severe prolapse necessitating emergency operation. The postoperative course was satisfactory.
Two cases of parathyroid tumours occurring in unusual situations are described. Such cases may cause difficulty in both the diagnosis and the surgical treatment of hyperparathyroidism. The cases described illustrate the importance of a definitive aetiological diagnosis in hypercalcaemia, if appropriate surgery is to be performed. The value of discriminant function analysis and hydrocortisone suppression tests are discussed.
In three patients with march haemoglobinuria a well-defined protein abnormality has been revealed by high-resolution sodium-dodecyl-sulphate/polyacrylamide-gel electrophoresis.
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Autologous bone marrow transplantation (ABMT) following intensive therapy regimes is being used increasingly in relapsed lymphomas. To date no randomised studies have been performed to ascertain the value of this form of therapy. We describe here our experience of ABMT in both Hodgkin's disease and Non-Hodgkin's Lymphoma and review the situations in which we believe future randomised studies should be based.
The British National Lymphoma Investigation (BNLI) has assessed the use of an IMVP-16 regimen (ifosfamide, methotrexate, VP-16) in 46 patients with high grade non-Hodgkin's lymphoma (NHL) who on first-line chemotherapy either failed to attain a complete remission or relapsed. Seventeen patients responded to IMVP-16 but only five (11 per cent) went into a complete remission (CR), 12 (26 per cent) had a partial remission (PR) and 29 (63 per cent) showed no response (NR). CR after IMVP-16 has been maintained in only one case (36 months). The results of this study imply that the use of this IMVP-16 protocol as second-line treatment for patients with recurrent high grade NHL is unsuccessful and alternative salvage regimens should be sought.
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While the terminal stages of erythroid differentiation are regulated by the hormone erythropoietin, the early stages of proliferation and differentiation of immature erythroid progenitor cells also depend on cellular factors functionally defined as burst-promoting activity (BPA). Thus, in vitro there is suboptimal development of primitive erythroid progenitor cells (burst-forming units--erythroid, BFU-E) into colonies unless a source of BPA is added. It has been demonstrated that T cells and monocytes produce BPA. Monocytes may represent the main source of BPA and the major role of T cells may be to augment BPA production by monocytes. Irradiated bone marrow cells, which contain T cells, monocytes and other BPA-producing cells, also promote BFU-E colony formation. As these studies used crude BFU-E populations as target cells, it was not possible to define which of the accessory cell products act directly on the progenitor cell. Here we have used a panel of monoclonal antibodies to purify BFU-E from peripheral blood. We demonstrate that BPA produced by both a monocyte and a T-cell line acts directly on the erythroid progenitor cell and can support colony formation by single BFU-E.
Expression of receptors for sheep red blood cells and the ability to proliferate in response to phytohaemagglutinin (PHA) are the traditional properties of human T cells, but the function of the sheep red cell receptor (the T11 antigen) is controversial and the mechanism of PHA-induced mitogenesis unclear. Mitogenesis involves a complex series of cell-mediated and factor-dependent interactions, but a rise in intracellular free calcium concentration, [Ca2+]i, seems to be an important primary event in T-cell activation. We have now investigated the effects of three monoclonal antibodies, previously shown to inhibit mitogen-induced proliferation, on T-cell [Ca2+]i. We find that anti-LFA-2 and OKT11, which react with the sheep red cell receptor, have no effect on [Ca2+]i, nor do they inhibit the rise in [Ca2+]i induced by concanavalin A (Con A) or the mitogenic anti-T3 monoclonal antibody UCHT1 (ref. 11). They do, however, block PHA-induced Ca2+ mobilization. Anti-LFA-1, which reacts with the lymphocyte function-associated antigen, has no effect on intracellular Ca2+. These studies suggest that the sheep red blood cell receptor is an activation pathway for T cells and that the effects of PHA are mediated through this pathway.
Interferon alfa-2a shows both antiviral and antitumoral activity, but its role in the treatment of many conditions remains controversial. It is, however, the treatment of choice for chronic, active hepatitis B, chronic hepatitis C and AIDS-related Kaposi's sarcoma, and is also effective in metastatic renal carcinoma and chronic myelogenous leukaemia. Optimal dose regimens are unclear, and further randomized trials are needed.