Cross-talk between T cells and NK cells generates rapid effector responses to Plasmodium falciparum-infected erythrocytes

J Immunol. 2010 Jun 1;184(11):6043-52. doi: 10.4049/jimmunol.1000106. Epub 2010 Apr 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Separation
  • Erythrocytes / parasitology*
  • Flow Cytometry
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology
  • Malaria, Falciparum / immunology*
  • Plasmodium falciparum / immunology
  • Receptor Cross-Talk / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism


  • Interleukin-2
  • Interferon-gamma