Systemic T-cell unresponsiveness during rush bee-venom immunotherapy.
By rush bee-venom immunotherapy, subjects reacting allergically to the venom can be effectively anergized, although the mechanism of action is not known. Here we analyzed the systemic effects of rush desensitization on the T cells of allergic patients. In most patients, we found reduced frequencies of T cells recalled to express CD69 and the cytokines interleukin (IL)-4 and interferon-gamma (IFN-gamma) after stimulation of peripheral blood mononuclear cells with phorbol 12-myristate 13-acetate (PMA) and ionomycin, as compared with normal donors. These frequencies are progressively reduced during immunotherapy. The frequency of cells expressing IL-2 does not change. A few patients show a different response to immunotherapy: frequencies of cells expressing CD69, IL-4, or IFN-gamma do not change, and remain similar to those of normal donors. However, the frequency of cells able to express IL-2 is increased. The analysis of cytokine expression in CD45RO+ vs CD45RO- T-cell populations revealed differences between normal and allergic donors. In allergic patients, higher frequencies of IL-4- and IFN-gamma-expressing cells among the CD45RO- subpopulation were found than in normal donors. This situation is not modified by immunotherapy. The results reveal a certain degree of heterogeneity in the response of allergic patients to bee-venom rush immunotherapy; however, all are clearly differentiated from normal controls as judged by cytokine expression of CD45RO- T cells. In most allergic patients, a considerable percentage of Th cells become unresponsive to mitogenic stimulation, and may be responsible for the desensitization itself.
Segura
J A
JA
Institute for Genetics, University of Cologne, Germany.
Assenmacher
M
M
Irsch
J
J
Hunzelmann
N
N
Radbruch
A
A
D000328:Adult; D000485:Allergens; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001514:Bee Venoms; D003888:Desensitization, Immunologic; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000628:therapy*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
D000485:Allergens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001514:Bee Venoms; D007371:Interferon-gamma; D007376:Interleukin-2; D015847:Interleukin-4; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D000099192:CD69 Antigens