The cellular lesion responsible for exaggerated IgE synthesis accompanying allergic breakthrough.
Appropriate levels of IgE are maintained by a cellular and molecular network composed of (1) a suppressive, Ly-1+, CD4+ T cell-dependent arm that is activated by inappropriate high levels of IgE and (2) an enhancing, CD8+ T cell-dependent arm that controls this suppression in a feedback regulatory manner. Ly-1+ T cells also function to counterbalance (inhibit) the activity of these latter CD8+ T cells. It has been previously shown that Ly-1+ T cells can reverse low-dose irradiation-induced enhancement of IgE antibody responses (i.e., allergic breakthrough). We have analyzed lymphocytes isolated from mice subjected to low-dose irradiation to determine which component of this network is defective in such animals. Stimulation of normal lymphocytes with IgE in vitro resulted in the release of lymphokines that suppress IgE antibody responses. In contrast, similar stimulation of lymphocytes from irradiated mice did not elicit secretion of such suppressive lymphokines, unless the cells were depleted of CD8+ T cells or reconstituted with normal Ly-1+ T cells. Because Ly-1+ T cells of irradiated mice could not reconstitute the response, we conclude that this functional subset of CD4+ T cells, which normally controls CD8+ T cell activity in this network, is defective in animals that exhibit irradiation-induced allergic breakthrough.
Marcelletti
J F
JF
Medical Biology Institute, La Jolla, California 92037.
Katz
D H
DH
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology; D016827:CD8 Antigens; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects
D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D016827:CD8 Antigens; D011961:Receptors, Fc; D017455:Receptors, IgE; D013491:Suppressor Factors, Immunologic; D007073:Immunoglobulin E