Naive human αβ T cells respond to membrane‐associated components of malaria‐infected erythrocytes by proliferation and production of interferon‐γ

Abstract

Crude extracts of Plasmodium falciparum schizont‐infected erythrocytes (PfSE) induce polyclonal activation of peripheral blood T lymphocytes from naive (malaria unexposed) humans. We demonstrate that the active component of PfSE is membrane bound, soluble in sodium dodecyl sulphate (SDS) and partially heat stable, but distinct from the tumour necrosis factor (TNF)‐inducing, exoantigen‐like activity of schizont extracts. Malaria pigment induces little or no T‐cell activation. The responding cells are predominately CD4+, CD45RO+, T‐cell receptor (TCR)αβ+. Contrary to previous reports, expansion of the TCRγδ+ subset was observed in cells from only one of eight donors. Proliferating cells secrete interferon‐γ (IFN‐γ) and release large amounts of soluble interleukin‐2R (sIL‐2R) into the culture supernatant but produce no detectable interleukin‐4 (IL‐4), a phenotype typical of the T‐helper (Th)1 subset of CD4+ T cells. We propose that these activated T cells may initiate the inflammatory response to malaria infection in non‐immunes and may contribute to the pathology of the disease.

Innate Immune Response to Malaria: Rapid Induction of IFN-γ from Human NK Cells by LivePlasmodium falciparum-Infected Erythrocytes

“…Responses tend to peak after 6 -7 days activation in vitro and the proliferating cells have been identified as either TCR␣␤ ϩ T cells, which respond in a classical MHC-restricted manner to both live and dead parasite Ags, or TCR␥␦ ϩ T cells that respond preferentially to live parasites (23,24); both cell types have also been shown to secrete IFN-␥ (21,23,25). Recently, it has been suggested that live P. falciparum can induce rapid (within 12-24 h) IFN-␥ and TNF-␣ responses (31) and that TCR␥␦ ϩ T cells may contribute to the early IFN-␥ response (32).…”

“…Regarding the human immune response to malaria, we and others have shown that PBMC from malaria-unexposed donors can produce IFN-␥ in response to stimulation by either live or dead schizont Ags (21)(22)(23)(24). Live parasites induce proliferation of both ␣␤ and ␥␦ TCR ϩ T cells, whereas dead schizont extract activates only TCR␣␤ ϩ T cells (24).…”

“…Live parasites induce proliferation of both ␣␤ and ␥␦ TCR ϩ T cells, whereas dead schizont extract activates only TCR␣␤ ϩ T cells (24). These cells have been widely assumed Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom to be the major source of IFN-␥ (23,25). Activation of TCR␣␤ ϩ T cells has been ascribed to reactivation of a polyclonal population of memory cells primed by exposure to cross-reactive Ags (21,26,27), whereas the TCR␥␦ ϩ T cell response is restricted to the V␥9V␦2 subset (28,29), and is induced by small, phosphorylated nonprotein Ags similar to those described for mycobacteria (30).…”

Age dependent characteristics of protection v. susceptibility to Plasmodium falciparum

“…This is consistent with a Th1-to Th2-like shift in immune responsiveness to chronic exposure to infection. Finally, naive a b T cells from non-imm une humans (the cells which would predom inate in younger persons; see above) produced IFN-g but not IL-4 in response to membrane components of red blood cells infected with P. falciparum (Dick et al, 1996).…”

Immunophenotyping of blood mononuclear cells from P. berghei (NK-65) infected and immunized BALB/c mice

“…T cells on D9 to D18 (PI). Dick et al (1996) revealed that the malaria antigens induced expansion of CD4 ? cells from malaria nonexposed individuals.…”