CD4(+) T cell responses to CD40-deficient APCs: Defects in proliferation and negative selection apply only with B cells as APCs

During T-APC interactions in vivo, interfering with CD40-CD154 interactions leads to reduced T cell priming, defects in effector function, and, in som e cases, T cell tolerance. As shown here, however, presentation of conventi onal peptide Ags by CD40-deficient spleen APC in vitro leads to normal CD4( +) T cell proliferative responses. By contrast, responses to the same pepti des presented by purified B cells were markedly reduced in the absence of C D40. Thus, the requirement for CD40-CD154 interactions appears to be strong ly influenced by the type of APC involved. Analysis of responses to endogen ous superantigens, which are known to be strongly dependent on B cells for presentation, indicated that CD4(+) responses to strong Ag are less depende nt on CD40 than are responses to weak Ags. Similar findings applied to nega tive selection in the thymus. Thus, deletion of potentially autoreactive ce lls depended on CD40 expression when B APC were involved, and this requirem ent was most pronounced when negative selection was directed to weak Ags.