All ETDs from UAB

Advisory Committee Chair

Sasanka Ramanadham

Advisory Committee Members

Rakesh Patel

Teresa Dilorenzo

Charles E Chalfant

Yuanyuan Li

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


We reported that Ca2+-independent phospholipase A2β (iPLA2) contributes to type 1 diabetes (T1D) development; however, the impact of lipid signaling from T-cells is unknown. To address this, we first administered splenocytes from NOD, NOD.iPLA2+/- (NOD.HET), or NOD.iPLA2-/- (NOD.KO) mice to 4-week-old NOD.scid recipients. As expected, T1D onset was rapid in NOD cell recipients and 100% by 12 weeks. However, onset was delayed by 1-3 weeks in NOD.HET or NOD.KO cell recipients and only 60% became diabetic, suggesting a role for T-cell iPLA2. Next, to establish importance of iPLA2 in CD4 or CD8 cells, purified cells were administered to NOD.scid mice. Recipients of NOD CD4++CD8+ T-cells reached 50% incidence within 6 weeks and 95% became diabetic by 30 weeks. In contrast, administration of NOD CD8+ + NOD.HET CD4+ or NOD CD4+ + NOD.HET CD8+ T-cells delayed onset by 10 weeks and 40-50% remained diabetes-free at 30 weeks. Further, production of select proinflammatory lipids by T-cells from the NOD.HET donors and their abundances in scid recipients of NOD.HET CD4 or CD8 cells were reduced, suggesting their importance to T1D development. Consistently, inhibition of select lipid signaling reduced production of IFN from NOD T-cells. These findings identify a requisite role for iPLA2-derived lipid signaling from T-lymphocytes in T1D development.



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