Lymphoproliferative responses to a merozoite surface antigen of Plasmodium falciparum: preliminary evidence for seasonal activation of CD8+/HLA-DQ-restricted suppressor cells

Abstract

SUMMARYWe have investigated the phenotype of human lymphocytes responding to a defined Plasmodium jalciparum malaria aniigcn in vitro. Cells were obuiined Irom the peripheral blood of malaria-immune donors from an endemic area of West Africa and were tested for proliferation in response lo cloned IViigmenis of a merozoivc surface protein ^Pf MSP I). DcpicVion and inhihiiion studies intiiciucd vh;.\i the majority of proliferating eells were CD4+ and restrieted by HLA-DR or -DQ. A proportion of responding cells appeared tobeCD8'. but [heir response was dependent on help from CD4' cells. In two donors there was evidence ihal low respoii.ses could bccnhiinced by removal of CD8 • cells and/ or blocking of antigen presentation by anti-HLA-DQ antibodies. This phenomenon was observed in eells collected during ihc wet (malaria transmission) season bul nol in cells collected ftom ihc same individual during ihe dry season.

Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission

“…The greater seasonal variation in the ''high exposure'' community compared with the ''low exposure'' community argues in favour of this, as do our functional data indicating that CD25 1 cells from malaria-exposed donors -but not from donors with little or no malaria exposure -specifically suppressed malaria antigen-induced cytokine responses in vitro. Moreover, these results support previous data showing expansion of malaria-specific T effector cell function at the end of the rainy season in The Gambia [44] as well as evidence for seasonal variation in malaria-specific cell-mediated immune suppression [45]. We are confident that differences in age, ethnicity, nutritional status or exposure to helminth infections do not explain our findings because these did not differ noticeably between the rural and urban communities.…”

“…Moreover, these results support previous data showing expansion of malaria-specific T effector cell function at the end of the rainy season in The Gambia [44] as well as evidence for seasonal variation in malaria-specific cell-mediated immune suppression [45]. We are confident that differences in age, ethnicity, nutritional status or exposure to helminth infections do not explain our findings because these did not differ noticeably between the rural and urban communities.…”

Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion

“…adami DS infection, as moderate levels of this cytokine (300-500 pg/ml) were detected in purified T cell cultures (data not shown). In early studies, CD8 + T cells have been involved in the down regulation of lymphoproliferative responses to native or recombinant malaria antigens (Riley et al, 1989;Mshana et al, 1990;Riley et al, 1993) and these cells are an important source of TGF-β during blood stage infection (Omer et al, 2003). The discrepancies between our results with total splenic cells, CD90and CD4 + cell cultures suggests that other cells besides CD4 + T cells and CD90lymphocytes are responsible for the high IL-10 response measured during lethal infection.…”

Differential Cellular Recognition of Antigens During Acute Plasmodium falciparum and Plasmodium vivax Malaria

“…The low proliferative reactivity in residents without clinical malaria suggests that long-lasting Pf MSP5-specific memory responses did not develop in these donors despite at least 2 years of P. falciparum exposure and high frequencies of antibodies to Pf MSP5 [9], albeit in a region of unstable rather than hyperendemic transmission [10]. Similarly low responsiveness has been reported to other malarial antigens [17–20], whereas studies from hyperendemic areas, especially those with seasonal transmission, show higher proliferation reactivity to malarial antigens [21–23] in individuals with life-long exposure. Together these studies highlight the broad diversity of T-cell responsiveness amongst different geographic areas with different malaria endemicity.…”