Plasmodium falciparum‐specific human T cell clones: evidence for helper and cytotoxic activities

Abstract

This report describes the isolation, and the phenotypic and functional characterization of Plasmodium falciparum-specific human T lymphocyte clones (TLC) obtained from 2 acutely infected and 4 clinically immune donors. Approximately one third of the TLC obtained from the acutely infected patients had the phenotype CD8+/CD4-. No such clones were obtained from the clinically immune donors. P. falciparum-specific, major histocompatibility complex-restricted CD8+ clones can lyse unrelated tumor cell targets in the presence of anti-CD3 antibodies, suggesting that these clones have cytotoxic potential. Conversely no killing was obtained with two CD4+ P. falciparum-specific TLC, even in the presence of anti-CD3 antibody, In addition the helper function of a CD4+ clone was demonstrated in a T/B cell cooperation system.

CD8 T-cell clones producing interleukin-5 and interferon-gamma in bronchial mucosa of patients with asthma induced by toluene diisocyanate.

“…This finding is different from the prev alent phenotype of clones derived from polyclonal mitogen-reactive T lymphocytes of human lung tissue of nonasthmati cs (15) or of bronchoalveol ar lavage cells of asthmatic and nonasthmatic subjects (16). The high percentage of CDS+ clones was surprising, considerin g the acknowledged difficulties associated with efficient cloning of CDS cell s (17). It is recognized that the cloning procedure may select certain type s of T cell s. Howe ver , the majority of the clones establi shed from allergic asthmatics with the same procedure 4S h after spec ific bronchial challenge were CD4+.…”

Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

“…Studies in rodents and humans immunized with irradiated sporozoites revealed that not only antibodies, but also CD4 and CD8 cells that exhibited cytotoxic T-cell (CTL) responses or produced cytokines such as interferon-␥ were important components of the protective immune network against the pre-erythrocytic stage of P. falciparum [22]. Target epitopes for these T-cells have been localized to the Cterminal region of the CSP [23][24][25][26]. The recognition that peptide sequences lying outside the CSP repeat were important for induction of humoral and cellular responses against the hepatic stage led to the inclusion of non-repeat portions of the molecule in the next generation of CSP-based vaccines.…”

Epitopes recognized by human t lymphocytes on malaria circumsporozoite protein

“…PBMC were stimulated for 6 days with peptide (10 pg/ml), expanded in interleukin 2 (IL 2)-containing medium and cloned in the presence of autologous PBMC and antigen as previously described [17]. To test antigen reactivity of the clones in a proliferative assay, cloned T cells (2 x lo4) were cocultured (in triplicate) with lo5 irradiated PBMC in 0.2 ml complete medium with or without antigen (flat-bottom well).…”