Functional cooperation between T helper cell determinants

The immune response to T helper (Th) cell determinants of a variety of anti gens is often poor and limits severely the potential efficacy of current th erapeutic measures through vaccination. Here, we report: that an immunologi cally silent tumor determinant can be rendered immunogenic if linked with a dominant determinant of a parasite antigen, suggesting the existence of fu nctional Th-Th cooperation in vivo. This phenomenon could be mimicked in pa rt by signaling either through CD40 to the antigen-presenting cells or thro ugh OX40 to the tumor-determinant reactive T cells, with maximal effects ob tained by combined anti-CD40 and anti-OX40 treatment in vivo. The data sugg est that CD4 T cells reactive with a dominant determinant provide help to o ther CD4 T cells through up-regulating the costimulatory ability of antigen -presenting cells, in much the same way as help for CD8 cells. CD4 help for CD4 T cells represents a new immunological principle and offers new practi cal solutions for vaccine therapy against cancer and other diseases in whic h antigenic help is limiting.