Disparate and necessary functions of sialophorin as costimulatory molecule for CD8+ T Cell responses in fungal vaccine immunity
Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B770
Abstract ID: 5128
Presenting Author:
Som G NANJAPPA , Associate Professor at Univ. of Illinois, Urbana-Champaign
Abstract:
Costimulatory molecules of T cells fine-tune the signaling for effective responses and are attractive targets for immunomodulation and therapeutics. The existing paradigm on costimulatory molecule sialophorin (CD43) for T cell homeostasis is its dominant negative role. However, in a mouse model of fungal vaccine immunity, we show that CD43 is essential for CD8+ T cell responses and disparately augmented antifungal IL-17+ve(Tc17) than IFNg+ve (Tc1) cells. Contrary to many costimulatory molecule effects, CD43 was dispensable for effector Tc17-cell proliferation but needed for their survival. Conversely, CD43-deficient Tc1 cells exhibited enhanced proliferation, suggesting its subset-specific regulatory role. Despite these disparate roles, CD43 significantly enhanced the Akt, mTOR, and HIF-1a pathway activation in both subsets. Modulating these pathways by mTORC1 inhibition or HIF-1a stabilization affected the T-cell responses that were CD43 dependent. Adoptive transfer of effector CD8+ T cells suggested the necessity of CD43 in Tc17 cell survival by sustaining Bcl-2 levels, reducing active Caspase 3, and stable transition into memory T cells. Interestingly, CD43-deficient CD8+ T cells portrayed higher CTLA-4 and CD28 levels. Thus, our findings challenge the existing paradigm of CD43 as a predominant negative regulator of T-cell responses, highlight it as a potential target for enhancing fungal immunity, and offer new insights into its dynamic costimulatory functions.
Disparate and necessary functions of sialophorin as costimulatory molecule for CD8+ T Cell responses during fungal vaccine immunity
Category
Poster and Podium (Block Symposium)