Specific Lymphocyte Reactivity

The lymphocyte transformation test has been extensively used for the detection of lymphocytes specifically allergized to drugs (Halpern et al. 1967 Rocklin and David 1971 Warrington et al. 1979). The assay, however, was found to be unsuitable for the demonstration of hypersensitivity to chloramphenicol (Dobozy et al. 1971). The reason for this lack of reactivity was attributed to the inhibition of protein synthesis by the antibiotic. Using C-labeled histones, Dobozy et al. (1971) found that chloramphenicol had little influence on the methylation of histones and that enhanced histone methylation could be observed in the cultures of lymphocytes obtained from chloramphenicol allergic patients compared with normal controls. The overall correlation was 100% and the test was recommended as being very useful. 

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It is now well established that ganglioside added to culture media can modulate lymphocyte reactivity Iri vitro. Previous studies demonstrated this phenomenon in murine systems(8,9,10), and the present studies show that human peripheral blood mononuclear cell responses to non-specific mitogens and allogeneic stimuli are similarly sensitive to exogenous gangliosides. In none of these systems does the effect appear to be due to a nonspecific toxic effect as cell viability and several biological phenomena remain intact(9). Furthermore, the degree of inhibition is dose dependent. 

F6. Fong, S., Gilbertson, T. A., Chen, P. P., Vaughan, J. H., and Carson, D. A., Modulation of human rheumatoid factor-specific lymphocyte responses with a cross-reactive anti-idiotype bearing the internal image of antigen. J. Immunol. 132, 1183-1189 (1984). 

Ronnau AC, Sachs B, von Schmiedeberg S, Hunzelmann N, Ruzicka T, Gleichmann E, Schuppe HC. Cutaneous adverse reaction to ciprofloxacin demonstration of specific lymphocyte prohferation and cross-reactivity to ofloxacin in vitro. Acta Derm Venereol 1997 77(4) 285-8. 

King CL, Medhat A, Malhotra I, et al. Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity. J Immuno 1996 156 4715-21. 

In recent years, interest has focused on the role of cell-mediated immune response in melanoma. Specific cell-mediated responses may play a role in tumor regression, but the role of specific cells such as cytotoxic T lymphocytes (CTLs) is not fully understood. Tumor-infiltrating lymphocytes (TILs) have been shown in vivo and in vitro to possess antitumor reactivity. TILs contain a large number of mature tumor-specific lymphocytes and have been a target for manipulation in immunotherapeutic approaches for melanoma. 

RCM-related T-cell activity may be assessed in vitro by lymphocyte transformation test [19, 24]. In addition, CD69 upregulation (lymphocyte activation test) was observed in patients with a positive lymphocyte transformation test [24, 39]. These tests appear to be a promising tool to identify drug-reactive T cells in the peripheral blood of patients with RCM-induced drug-hypersensitivity reactions. However, the sensitivity and specificity remain unknown and, therefore, these tests cannot be recommended for routine use yet, but further research on the specificity and sensitivity is indicated. 

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