AGE-DEPENDENT APPEARANCE OF NONMAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED HELPER T-CELLS

T cells which recognize antigen in association with self major histoco mpatibility complex (MHC) molecules are positively selected within the thymus. This results in skewing of the T-cell repertoire toward the r ecognition of antigenic peptides presented by self MHC molecules. Whil e the thymus gland involutes at a relatively young age, bone marrow fu nction and the size of the peripheral T-cell pool are maintained with age. We have investigated the MHC restriction of helper T-cell functio n for B-cell production of specific antibody in mice of different ages . Splenic helper T cells from 2- to 3-month old mice immunized with ph osphocholine-keyhole limpet hemocyanin conjugate were MHC-restricted a s defined by their capacity to induce phosphocholine-specific antibody synthesis by syngeneic but not by allogeneic B cells. In contrast, sp lenic T cells from immunized 18- to 20-month-old mice induced specific anti-phosphocholine antibodies by both syngeneic and allogeneic B cel ls. No evidence of polyclonal immunoglobulin synthesis was detected. T he ability of T cells from old mice immunized with phosphocholine-keyh ole limpet hemocyanin to induce phosphocholine-specific antibody synth esis by B cells from allogeneic mice was inhibited by T cells from imm unized young mice. These findings suggest that non-MHC-restricted T-ce ll helper activity in old mice results from the loss of T cells, prese nt in young mice, which suppress non-MHC-restricted helper cells.