LIFE-SPANS OF HUMAN T-CELL RESPONSES TO DETERMINANTS FROM THE CIRCUMSPOROZOITE PROTEINS OF PLASMODIUM-FALCIPARUM AND PLASMODIUM-VIVAX

The longevity of specific human memory T-cell responses is largely unk nown. However, a knowledge of the duration of memory is important for understanding immunity to an organism and for planning vaccine interve ntion. To address this, we have examined T-cell memory to malaria by d etermining T-cell responses by subjects recently exposed to peptides s panning the circumsporozoite (CS) proteins of two species of malaria-c ausing organisms, Plasmodium falciparum and Plasmodium vivax. Response s to vivax CS peptides by exposed Thai subjects were more frequent tha n responses by nonexposed individuals, permitting identification of de terminants seen by vivax-induced responses. At the population level, t here appears to be life-long memory, as the time since individuals wer e exposed did not diminish responsiveness to these determinants. In co ntrast, falciparum-exposed subjects were largely indistinguishable fro m nonexposed controls in responsiveness to falciparum CS determinants. However, a single peptide (F16: DNEKLRKPKHKKLKQPGDGN) was recognized significantly more frequently by P. falciparum-exposed than nonexposed Thai subjects. T cells responsive to this peptide were CD450(+) and p roduced gamma-interferon. In contrast to the response to the vivax det erminants and the other falciparum determinants, responsiveness to F16 was undetectable or minimal 2 years after exposure. Our data provide the average life-spans of certain malaria-specific T cells and are con sistent with, but do not prove, the hypothesis that antigenic persiste nce (in the form of P. vivax hypnozoites) correlates with persistence of human T-cell memory.