Deletion of the Dense Core Vesicle Proteins IA-2 and IA-2β Causes Profound Leukopenia in Mice

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.60-60.16
• Main Authors: Gunti, Sreenivasulu, Gottumukkala, Raju VSRK, Carmona, Gilberto N, Notkins, Abner Louis
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.60.16

Previous studies showed that deletion of the genes encoding the dense core vesicle (DCV)-associated proteins IA-2 and/or IA-2β resulted in a decrease in the secretion of a number of hormones and neurotransmitters and that this, in turn, led to a variety of pathophysiologic and behavioral abnormalities. The effect of the deletion of these genes on the immune system has never been studied. In the present experiments, we found that the knockout of the IA-2 and IA-2β genes (double knockout) resulted in a profound leukopenia characterized by a 78% decrease in WBCs and an 84% decrease in absolute number of lymphocytes. The leukopenia was detected within 1.5 months after birth and persisted for at least 12 months. Both B and T cells were decreased by about 40–50% in bone marrow and thymus and by about 75% in the spleen. LPS-induced cytokine secretion (e.g., IL-6, MCP-1, INF-γ and TNF-α) also was severely impaired. The most likely explanation for these profound immunological abnormalities in single and double knockout mice is that they represent secondary events resulting from impaired secretion of hormones and neurotransmitters that are involved in immunological homeostasis.