Journal article
Plasmodium-host interactions directly influence the threshold of memory CD8 T cells required for protective immunity
The Journal of immunology (1950), Vol.186(10), pp.5873-5884
05/15/2011
DOI: 10.4049/jimmunol.1100194
PMCID: PMC3087867
PMID: 21460205
Abstract
Plasmodium
infections are responsible for millions of cases of malaria and about one million deaths annually. Recently, we showed that sterile protection (95%) in BALB/c mice required
P. berghei
circumsporozoite (CS
252-260
)-specific memory CD8 T-cells exceeding a threshold of ≥1% of all PBL. Importantly, it is not known if
Plasmodium
species affect the threshold of CS-specific memory CD8 T-cells required for protection. Furthermore, C57BL/6 mice immunized with radiation attenuated parasites are more difficult to protect against
Plasmodium
sporozoite challenge than similarly immunized BALB/c mice, however, it is not known if this is the result of different CD8 T-cell specificity, functional attributes of CD8 T-cells or mouse strain-specific factors expressed in non-hematopoietic cells. Here, we show more CS-specific memory CD8 T-cells are required for protection against
P. yoelii
sporozoite challenge than for protection against
P. berghei
sporozoite challenge. Furthermore,
P. berghei
CS
252
-specific CD8 T-cells exhibit reduced protection against
P. berghei
sporozoite challenge in the context of C57BL/6 and C57BL/10 non-MHC-linked genes in CB6F1 and B10.D2 mice, respectively. Generation and immunization of reciprocal chimeric mice between BALB/c and B10.D2 strains revealed that B10 background factors expressed by non-hematopoietic cells increased the threshold required for protection through a CD8 T-cell extrinsic mechanism. Finally, reduced CS-specific memory CD8 T-cell protection in
P. yoelii
infected BALB/c or
P. berghei
infected B10.D2 mice correlated with increased rates of
Plasmodium
amplification in the liver. Thus, both
Plasmodium
species and strain-specific background genes in non-hematopoietic cells determine the threshold of memory CD8 T-cells required for protection.
Details
- Title: Subtitle
- Plasmodium-host interactions directly influence the threshold of memory CD8 T cells required for protective immunity
- Creators
- Nathan W Schmidt - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USANoah S Butler - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USAJohn T Harty - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.186(10), pp.5873-5884
- DOI
- 10.4049/jimmunol.1100194
- PMID
- 21460205
- PMCID
- PMC3087867
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI085515-01A1 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID F32 AI084329-01 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 05/15/2011
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984001139302771
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