Induction of hapten-specific tolerance of human CD8+ urushiol (poison ivy)-reactive T lymphocytes.
The interaction of CD28 with B7 molecules (CD80 or CD86) is an essential second signal for both the activation of CD4+ T cells through the T-cell receptor and the prevention of anergy. We studied the requirement of hapten-specific human CD8+ cells for CD28 co-stimulation in recognition of hapten, and anergy induction. Urushiol, the immunogenic hapten of poison ivy (Toxicodendron radicans), elicits a predominantly CD8+ T-cell response. Autologous PBMC were pre-incubated with urushiol prior to fixation by paraformaldehyde. Fixed antigen-presenting cells were unable to present urushiol to human CD8+ urushiol-specific T cells. Addition of anti-CD28, however, overcame this antigen-presenting defect, enabling CD8+ cells to proliferate. Fixation of antigen-presenting cells prevents upregulation of B7, and addition of anti-CD28 substitutes for this signal. Proliferation of CD8+ T cells in response to urushiol was blocked by CTLA4Ig, a recombinant fusion protein that blocks CD28/B7 interactions. Preincubation of urushiol-specific CD8+ cells with fixed PBMC + urushiol for 7 d induced anergy. Anergic CD8+ cells were viable and able to proliferate in response to IL-2, but not in response to urushiol. Induction of anergy required the presence of urushiol, and pre-incubation with irradiated PBMC + urushiol did not have this effect. It is proposed that anergy was induced by presentation of urushiol by fixed PBMC, in the absence of adequate co-stimulation signals. Induction of anergy by blocking of co-stimulation could potentially induce clinical hyposensitization to haptens.
Kalish
R S
RS
Department of Dermatology, State University of New York @ Stony Brook, 11794-8165, U.S.A.
Wood
J A
JA
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology*; D060908:CTLA-4 Antigen; D002396:Catechols / Q000032:analysis / Q000276:immunology; D002460:Cell Line; D017635:Clonal Anergy / Q000187:drug effects; D005404:Fixatives; D005557:Formaldehyde / Q000494:pharmacology; D006241:Haptens / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D010641:Phenotype; D010947:Plants, Toxic / Q000502:physiology; D011108:Polymers / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D002396:Catechols; D005404:Fixatives; D006241:Haptens; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D011108:Polymers; D005557:Formaldehyde; C003747:urushiol; D000069594:Abatacept; C003043:paraform