Figure 5. Differential autoreactive functional responses by human OCH^HIGH and OCH^LOW iNKT clones.

Matched pairs of human OCH^HIGH (red columns and markers) and OCH^LOW (blue columns and markers) iNKT clones were compared for their ability to proliferate, secrete cytokines, and exhibit cytotoxicity in response to lipid-pulsed or endogenous lipid presenting CD1d-positive antigen presenting cells. (A) Proliferation of three representative pairs of OCH^HIGH and OCH^LOW iNKT clones from different healthy donors in response to K7-, OCH-, or vehicle-pulsed human CD1d-expressing T2 cells (T2-CD1d) or to K7-pulsed CD1d negative T2 cells (T2-) is shown. OCH^HIGH clones consistently displayed greater proliferation than OCH^LOW clones in response to OCH or vehicle pulsed T2-CD1d. cpm, counts per minute. Mean values ± s.e.m. are shown. (B) Cytokine secretion profiles of a representative pair of matched OCH^HIGH and OCH^LOW iNKT clones in response to the strong agonist ligand K7 and the partial agonist ligand OCH, presented by T2-CD1d, are shown. OCH^HIGH iNKT clones exhibited much stronger cytokine secretion than OCH^LOW iNKT cells in response to OCH-pulsed T2-CD1d, while cytokine secretion was similar for both in response to K7-pulsed T2-CD1d. (C) Autoreactive cytokine release in response to T2-CD1d in the absence of added exogenous ligands is shown for four matched pairs of OCH^HIGH and OCH^LOW iNKT clones. OCH^HIGH but not OCH^LOW iNKT clones consistently exhibited substantial autoreactive cytokine secretion. (D) Specific lysis of K7- (filled markers) and OCH- (unfilled markers) pulsed T2-CD1d targets is shown for three matched pairs of OCH^HIGH and OCH^LOW iNKT clones from different donors.