FUNCTIONAL CHARACTERIZATION AND MECHANISTIC STUDIES OF A FUNGAL IMMUNOMODULATORY PROTEIN-FVE ON MURINE T CELLS

Abstract

FUNGAL IMMUNOMODULATORY PROTEIN (FIP)-FVE PLAYS IMMUNOMODULATORY ROLES IN TUMOR IMMUNOLOGY AND ALLERGY. HOWEVER, A COMPREHENSIVE MECHANISM BY WHICH FIP-FVE MODULATES THE IMMUNE RESPONSE REMAINS UNCLEAR. OUR IN VITRO RESULTS SUGGESTED THAT FIP-FVE COULD DIRECTLY UP-REGULATE CD69, CD25, CD137 (4-1BB), CD27, AND CD28 EXPRESSIONS ON MOUSE T CELLS. MOREOVER, BINDING OF CD70 AND OX-40L WITH THEIR COGNATE RECEPTORS ON T CELLS WAS ALSO REQUIRED TO INDUCE OPTIMAL T CELL PROLIFERATION AND SECRETION OF CYTOKINE/CHEMOKINE. BOTH MAGNITUDE AND FUNCTION OF ANTIGEN-SPECIFIC IMMUNE RESPONSES WERE ENHANCED WHEN OT-I CD8+ T CELLS WERE PRE-STIMULATED WITH FIP-FVE. FOOTPAD INJECTION OF FIP-FVE INTO MICE LED TO INCREASED NUMBER OF PROLIFERATING T CELLS AND RECRUITMENT OF OTHER LYMPHOCYTES INTO DRAINING LYMPH NODES. ALSO, CO-ADMINISTRATION OF FIP-FVE AND OVA PEPTIDE IN MICE INCREASED THE NUMBER AND PERCENTAGE OF ANTIGEN-SPECIFIC CD8+ T CELLS IN VIVO. THUS, FIP-FVE MAY FUNCTION AS AN ADJUVANT VIA ACTIVATION A