PUBLICATION
First Demonstration of Antigen Induced Cytokine Expression by CD4-1+ Lymphocytes in a Poikilotherm: Studies in Zebrafish (Danio rerio)
- Authors
- Yoon, S., Mitra, S., Wyse, C., Alnabulsi, A., Zou, J., Weerdenburg, E.M., van der Sar, A.M., Wang, D., Secombes, C.J., Bird, S.
- ID
- ZDB-PUB-150618-2
- Date
- 2015
- Source
- PLoS One 10: e0126378 (Journal)
- Registered Authors
- van der Sar, Astrid M., Zou, Jun
- Keywords
- Zebrafish, Cytokines, Lymphocytes, T cells, Kidneys, White blood cells, Gene expression, Polymerase chain reaction
- MeSH Terms
-
- Adaptive Immunity
- Amino Acid Sequence
- Animals
- Antibodies/chemistry
- CD4-Positive T-Lymphocytes/classification
- PubMed
- 26083432 Full text @ PLoS One
Abstract
Adaptive immunity in homeotherms depends greatly on CD4+ Th cells which release cytokines in response to specific antigen stimulation. Whilst bony fish and poikilothermic tetrapods possess cells that express TcR and CD4-related genes (that exist in two forms in teleost fish; termed CD4-1 and CD4-2), to date there is no unequivocal demonstration that cells equivalent to Th exist. Thus, in this study we determined whether CD4-1+ lymphocytes can express cytokines typical of Th cells following antigen specific stimulation, using the zebrafish (Danio rerio). Initially, we analyzed the CD4 locus in zebrafish and found three CD4 homologues, a CD4-1 molecule and two CD4-2 molecules. The zfCD4-1 and zfCD4-2 transcripts were detected in immune organs and were most highly expressed in lymphocytes. A polyclonal antibody to zfCD4-1 was developed and used with an antibody to ZAP70 and revealed double positive cells by immunohistochemistry, and in the Mycobacterium marinum disease model CD4-1+ cells were apparent surrounding the granulomas typical of the infection. Next a prime-boost experiment, using human gamma globulin as antigen, was performed and revealed for the first time in fish that zfCD4-1+ lymphocytes increase the expression of cytokines and master transcription factors relevant to Th1/Th2-type responses as a consequence of boosting with specific antigen.
Errata / Notes
Correction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping