Cross-talk between T cells and NK cells generates rapid effector responses to Plasmodium falciparum-infected erythrocytes.
Rapid cell-mediated immune responses, characterized by production of proinflammatory cytokines, such as IFN-gamma, can inhibit intraerythrocytic replication of malaria parasites and thereby prevent onset of clinical malaria. In this study, we have characterized the kinetics and cellular sources of the very early IFN-gamma response to Plasmodium falciparum-infected RBCs among human PBMCs. We find that NK cells dominate the early (12-18 h) IFN-gamma response, that NK cells and T cells contribute equally to the response at 24 h, and that T cells increasingly dominate the response from 48 h onward. We also find that although gammadelta T cells can produce IFN-gamma in response to P. falciparum-infected RBCs, they are greatly outnumbered by alphabeta T cells, and thus, the majority of the IFN-gamma(+) T cells are alphabeta T cells and not gammadelta T cells; gammadelta T cells are, however, an important source of TNF. We have previously shown that NK cell responses to P. falciparum-infected RBCs require cytokine and contact-dependent signals from myeloid accessory cells. In this study, we demonstrate that NK cell IFN-gamma responses to P. falciparum-infected RBCs are also crucially dependent on IL-2 secreted by CD4(+) T cells in an MHC class II-dependent manner, indicating that the innate response to infection actually relies upon complex interactions between NK cells, T cells, and accessory cells. We conclude that activation of NK cells may be a critical function of IL-2-secreting CD4(+) T cells and that standard protocols for evaluation of Ag-specific immune responses need to be adapted to include assessment of NK cell activation as well as T cell-derived IL-2.
Horowitz
Amir
A
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Newman
Kirsty C
KC
Evans
J Henry
JH
Korbel
Daniel S
DS
Davis
Daniel M
DM
Riley
Eleanor M
EM
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D004912:Erythrocytes / Q000469:parasitology*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology; D020239:Receptor Cross-Talk / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D007371:Interferon-gamma