Cytolytic activity of CD4+ and CD8+ T lymphocytes in plasmodium falciparum malaria susceptible and resistant individuals in a malaria endemic area of western Kenya

Abstract

Acquired immunity in malaria is both species and stage-specific, with both B- and T-cells being involved. Cell-mediated immunity by T-cells involves cytokine production and the direct killing of infected hepatocytes and/or sporozoites. This cytolytic ability is effected by cytotoxic T lymphocytes (CTL). One epitope recognized by the CTL (Th3R) spans the amino-acid sequence 368-390 of the circumsporozoite (CS) protein on the surface of the sporozoites and infected hepatocytes. This epitope has significant antigen diversity, thus posing a potential problem in producing a pre-erythocytic vaccine.

In this study, peripheral blood lymphcytes (PBL) from adult male residents of a malaria endemic area were expanded for six days using rIL-2 and malaria synthetic peptides representing the 368-390 amino-adi sequence of the Plasmodium falciparum CS protein. The effector cells were then tested against Epstein-Barr virus (EBV) lymphblastoid targets pulsed with or without the peptides. Malaria specific lysis was determined as the difference between lysis in the presence of a peptide and lysis in the absence of a peptide. Specific lysis of 10% or more was considered as a positive response. Samples from 40 individuals were assayed. Ten individuals (25%) showed CTL activity, 13 individuals (32.5 %) showed negative responses and the remaining individuals (42.5%) had 'indeterminate' results. There was no relationship between CTL responses and susceptibility or resistance to P. falciparum re-infection (U=61.5; U0.05(2) 9,13=89; P>0.1). However, there was cross-reactivity of the 368-390 peptide variants. The CTL responses were MHC-restricted, with the short peptide 127 (368-379) being the optimal size for the CTL epitope.