Life-spans of human T-cell responses to determinants from the circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax.

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RESUMO

The longevity of specific human memory T-cell responses is largely unknown. However, a knowledge of the duration of memory is important for understanding immunity to an organism and for planning vaccine intervention. To address this, we have examined T-cell memory to malaria by determining T-cell responses by subjects recently exposed to peptides spanning the circumsporozoite (CS) proteins of two species of malaria-causing organisms, Plasmodium falciparum and Plasmodium vivax. Responses to vivax CS peptides by exposed Thai subjects were more frequent than responses by nonexposed individuals, permitting identification of determinants seen by vivax-induced responses. At the population level, there appears to be life-long memory, as the time since individuals were exposed did not diminish responsiveness to these determinants. In contrast, falciparum-exposed subjects were largely indistinguishable from 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 produced gamma-interferon. In contrast to the response to the vivax determinants 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 consistent with, but do not prove, the hypothesis that antigenic persistence (in the form of P. vivax hypnozoites) correlates with persistence of human T-cell memory.

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