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- Title
Induction of Hapten Specific Tolerance of Human CD8+ Urushiol (Poison Ivy)-Reactive T Lymphocytes.
- Authors
Kalish, Richard S.; Wood, Jonathan A.
- Abstract
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 CDS+ cells for CD28 co-stimulation in recognition of hapten, and anergy induction. Urushiol, the immunogenic hapten of poison ivy (<em>Toxicodendron radicans</em>), 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 antilCD28 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.
- Subjects
T cells; CELL receptors; ANTIGENS; IMMUNITY; HAPTENS; ALLERGENS; LYMPHOCYTES; BINDING sites
- Publication
Journal of Investigative Dermatology, 1997, Vol 108, Issue 3, p253
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12286447