Lymphocyte transformation factor

A 60-year-old woman with normal liver function tests developed acute hepatitis 6 weeks after starting to take gliclazide. No viruses, autoimmune factors, or metabolic factors that could have caused hepatitis could be found. A lymphocyte transformation test was not performed. A liver biopsy was compatible with drug-related acute hepatitis. When gliclazide was withdrawn she improved. She took glibenclamide and recovered fully within 6 weeks. 

When a patient suffers from a certain autoimmune disease and one suspects the person to be exposed to a certain environmental factor, few possibilities exist to prove exposure. Several in vitro or in vivo tests, such as skin tests, serological tests, and the lymphocyte transformation test (LTT), can be performed to demonstrate a sensitization to a certain chemical (Choquet-Kastylevsky et al., 2001 Pichler, 2003). 

Watson KC, Joubert SM, Bennett MA (1961) Some factors influencing the hemagglutination of penicillin-sensitized erythrocytes. Immunology 4 193 Webster AW, Thompson RA (1974) The ampicillin rash. Lymphocyte transformation by ampicillin polymer. Clin Exp Immunol 18 553 Weidemiiller HL, Ziegler W (1970) On the proteinaceous impurity of penicillin. Arzneim Forsch 20 585... 

Back et al. (1977) found the lymphocyte transformation test positive in ten of 18 patients hypersensitive to nitrofurantoin. Pearsell et al. (1974) observed lymphocyte hypersensitivity and a lymphocyte migratory inhibitory factor in one patient who had an acute pulmonary syndrome with simultaneous skin allergy after nitrofurantoin. This hypersensitivity was seen for 2 Vi years and a participation of the T-lymphocytes rather than of the B-lymphocytes in the hypersensitivity is supposed. The authors suppose that a cellular mechanism is responsible for the hypersensitivity to nitrofurantoin. 

Beatty, D, W, and Dowdle, E, B. (1978) The effects of kwashiorkor serum of factors required for optimal lymphocyte transformation ylt ro, Clin, Exp, Immunol. 35 433. 

Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS (1986) Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med 163 1037-1050... 

Bertone S, Schiavetti F, Bellomo R, Vitale C, Ponte M, Moretta L, Mingari MC Transforming growth factor-p-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes. Eur J Immunol 1999 29 23. 

An immunologic basis for chronic beryllium disease has been postulated and a hypersensitivity phenomenon demonstrated. Consistent with the concept of chronic berylliosis as a hypersensitivity pulmonary reaction are the following Persons with berylliosis also show delayed cutaneous hypersensitivity reactions to beryllium compounds their peripheral blood lymphocytes undergo blast transformation and release of macrophage inhibition factor after exposure to beryllium in vitro helper/suppressor T-cell ratios are depressed and there is lack of a dose-response relationship in chronic beryllium cases. Hypersensitization may lead to berylliosis in people with relatively low exposures, whereas nonsensitized individuals with higher exposures may have no effects. 

The production yields of human monoclonals upon immortalization of the human B lymphocyte (by whatever means) are also low. Recoveries of 10-20 /ig per 10 transformed cells are not unusual. Such figures are approximately 10-fold lower than production levels of murine monoclonals. In addition, immortalized human B lymphocytes grow to a much lower cell density than that achievable with its murine counterpart. These latter factors render the production of human monoclonals an expensive process. 

Interleukin-4 (IL-4), cooperating with IL-21,227a stimulates growth of activated B cells, T lymphocytes, and mast cells, induces formation of cytotoxic CD8+ T cells, and enhances formation of IgG 228/229 The transforming growth factor-P (TGF-P) is another cytokine that modulates the development of the immune system. It affects a very broad range of tissues and is discussed in Chapter 32. 

In contrast, intracellular organisms (eg, mycobacterium species) elicit the production of THl cytokines, which lead to the activation of effector cells such as macrophages. A less well defined T cell subset (TH3) has been described that produces transforming growth factor-6 (TGF-B), whose numerous functions include down-regulation of proliferation and differentiation of T lymphocytes. 

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