Differences in the regulation of CD4 and CD8 T-cell clones during immune responses.

The functional units of immune response are lymphocyte clones. Analysis of lymphocyte life span in vivo shows that the overall turnover of CD4 and CD8 lymphocytes does not differ greatly. Recently, molecular methods have been developed which allow a global analysis of T-cell clones responding to an antigen in vivo. We have used a sensitive, modified heteroduplex analysis to follow T-cell clones responding to Epstein-Barr virus in acute infectious mononucleosis (AIM). Strikingly, all the many large clones detected in freshly isolated AIM blood were found within the CD8 fraction. CD4 clonal populations responding to the soluble recall antigen tetanus toxoid could only be detected after in vitro re-stimulation. These data imply that CD4 responses may be more polyclonal than those of CD8 cells and that the size of CD4 clones is more tightly regulated. Several molecular mechanisms may contribute to this. Up-regulation of telomerase allows very large expansions of CD8 cells to occur without exhaustion of proliferative capacity.