Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin4 (IL-4)-producing Th2 cells, or cure may result by Thl cells secreting gamma interferon (IFN-y). The present study examined the potential of human T cells to generate Thl or Th2 responses to L. donovani. The profiles of IFN-y, ILA4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel ofL. donovani-reactive CD4+ human T-celi clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-y, seven clones produced both IFN-y and IL-4, and eight produced only IFN'y. This is the first report of a Thland Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of ILH4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-'y-producing Thl cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.

Frequencies and absolute numbers of peripheral T-cell subsets were monitored closely following acute Plasmodium falciparum malaria in 22 Ghanaian children from an area of hyperendemicity for seasonal malaria transmission. The children presented with cerebral or uncomplicated malaria (CM or UM, respectively) or with severe malarial anemia. For all patients the frequencies and absolute numbers of peripheral T cells were lower than normal during the acute stage of disease. This lowering was most pronounced in the CM group and least pronounced in the UM group. Of particular interest, the CM patients showed markedly reduced frequencies of CD4 ؉ cells, the number of which also normalized slower than in the other clinical groups. In all patients, the T-cell frequencies gradually approached normal values after the initiation of therapy, whereas the absolute numbers rapidly reverted from lower than normal to higher than normal before returning to steady-state levels. Furthermore, the initially reduced T-cell surface density of the T-cell receptor/CD3 complex, which rapidly normalized, was a general finding for all three clinical groups, suggesting a state of peripheral T-cell hyporesponsiveness during acute malaria. The data presented suggest a rapid therapyinduced reemergence of T cells that had been temporarily removed from the peripheral circulation as a consequence of the malaria attack and that the degree of the disease-induced T-cell reallocation correlates with disease severity.

The 19-kDa conserved C-terminal part of the Plasmodium falciparum merozoite surface protein 1 (PfMSP1 19 ) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP1 19 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathione S-transferase-PfMSP1 19 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP1 19 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP1 19 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP1 19 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP1 19 and clinical protection against malaria.