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Requirement of CD28-CD86 costimulation for allergen-specific T cell proliferation and cytokine expression
R J Van Neerven1, M M Van de Pol, J S Van der Zee
1Laboratory of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands.
Background:
Allergen-specific T lymphocytes biased to the production of type 2 cytokines play an important role in the pathophysiology of atopic disease. It is not known whether optimal activation of these T cells requires costimulation via interaction of B7 (CD86/CD80) with CD28.
Methods:
Peripheral blood mononuclear cells (PBMC), isolated from 10 house dust mite Dermatophagoides pteronyssinus (Der p)-allergic asthma patients and 10 non-allergic control individuals, were stimulated with house dust mite (Der p) and the control antigens Candida albicans (CA) and tetanus toxoid (TT). The role of costimulation in activation for proliferation and cytokine mRNA production of peripheral blood T cells was studied by blocking CD28, CTLA-4, and their ligands CD80 (B7-1) and CD86 (B7-2).
Results:
The proliferation and the production of type 1 and 2 cytokine mRNA by T cells in response to Der p as well as the control antigens TT and CA was inhibited by simultaneously masking CD80 and CD86 using CTLA4-Ig, a soluble form of CTLA-4. Notably, Der p-specific proliferation of T cells from Der p-allergic asthma patients and non-allergic controls were inhibited equally well. Additional experiments with MoAbs revealed that activation of these T cells was optimally inhibited by blocking the interaction of CD28 with CD86.
Conclusion:
In vitro responses of allergen- and antigen-specific T cells of allergic patients and non-allergic control persons are equally dependent on costimulation via the CD28-CD86 pathway, suggesting that inhibition of this pathway may prevent complete activation of allergen-specific T cells in allergic individuals in vivo.