ZFIN ID: ZDB-PUB-150618-2
First Demonstration of Antigen Induced Cytokine Expression by CD4-1+ Lymphocytes in a Poikilotherm: Studies in Zebrafish (Danio rerio)
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.
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
  • CD4-Positive T-Lymphocytes/immunology*
  • CD4-Positive T-Lymphocytes/microbiology
  • CD4-Positive T-Lymphocytes/pathology
  • Cytokines/biosynthesis*
  • Cytokines/immunology
  • Genetic Loci/immunology
  • Histocompatibility Antigens Class II/genetics
  • Histocompatibility Antigens Class II/immunology*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium Infections, Nontuberculous/genetics
  • Mycobacterium Infections, Nontuberculous/immunology*
  • Mycobacterium Infections, Nontuberculous/microbiology
  • Mycobacterium Infections, Nontuberculous/veterinary*
  • Mycobacterium marinum/immunology
  • Phylogeny
  • RNA, Messenger/genetics
  • RNA, Messenger/immunology*
  • Sequence Alignment
  • Th1-Th2 Balance
  • ZAP-70 Protein-Tyrosine Kinase/genetics
  • ZAP-70 Protein-Tyrosine Kinase/immunology
  • Zebrafish/classification
  • Zebrafish/genetics
  • Zebrafish/immunology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/immunology
  • gamma-Globulins/administration & dosage
PubMed: 26083432 Full text @ PLoS One
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.