Phenotypic characterization of Plasmodium berghei responsive CD8+ T cells after immunization with live sporozoites under chloroquine cover

Malaria Journal

Research

Jittawadee Murphy¹  Jason H Richardson¹  Christian F Ockenhouse²  Edwin Kamau²  Clara Brando³ 

[1] Entomology Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, 20910, Silver Spring, MD, USA;Military Malaria Research Program, Malaria Vaccine Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, 20910, Silver Spring, MD, USA;Military Malaria Research Program, Malaria Vaccine Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, 20910, Silver Spring, MD, USA;Entomology Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave, 20910, Silver Spring, MD, USA;

关键词: Malaria;    Protective Antibody;    Plasmodium Berghei;    Irradiate Sporozoite;    Residual Protective Effect;   

DOI  :  10.1186/1475-2875-13-92

 received in 2013-09-12, accepted in 2014-02-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundAn effective malaria vaccine remains elusive. The most effective experimental vaccines confer only limited and short-lived protection despite production of protective antibodies. However, immunization with irradiated sporozoites, or with live sporozoites under chloroquine cover, has resulted in long-term protection apparently due to the generation of protective CD8+ T cells. The nature and function of these protective CD8+ T cells has not been elucidated. In the current study, the phenotype of CD8+ T cells generated after immunization of C57BL/6 mice with live Plasmodium berghei sporozoites under chloroquine cover was investigated.MethodsFemale C57BL/6 mice, C57BL/6 mice B2 macroglobulin −/− [KO], or invariant chain−/− [Ic KO] [6–8 weeks old] were immunized with P. berghei sporozoites and treated daily with 800 μg/mouse of chloroquine for nine days. This procedure of immunization is referred to as “infection/cure”. Mice were challenged by inoculating intravenously 1,000 infectious sporozoites. Appearance of parasitaemia was monitored by Giemsa-stained blood smears.ResultsBy use of MHC I and MHC II deficient animals, results indicate that CD8+ T cells are necessary for full protection and that production of protective antibodies is either CD4+ T helper cells dependent and/or lymphokines produced by CD4 cells contribute to the protection directly or by helping CD8+ T cells. Further, the phenotype of infection/cure P. berghei responsive CD8+ T cells was determined to be KLRG1high CD27low CD44high and CD62Llow.ConclusionThe KLRG1high CD27low CD44high and CD62Llow phenotype of CD8+ T cells is associated with protection and should be investigated further as a candidate correlate of protection.

【 授权许可】

Unknown   
© Brando et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.