IMMUNOGLOBULIN-LIKE TRANSCRIPT (ILT) RECEPTORS AS CD8 ANTAGONISTS

摘要

Compositions and methods for inhibiting effector CD8+ T cell priming by Langerhans cells (LCs), together with promotion of the production of IL-4 and IL-10 are disclosed herein. The findings of the present indicate that immunoglobulin-like transcript (ILT) inhibitory receptors expressed on dermal CD14+ DCs represent natural counterparts of the anti-CD8 mAbs. Accordingly, blocking ILT2 or ILT4 on dermal CD14⁺ DCs enhanced the generation of effector polyfunctional CD8⁺ T cells. Conversely, soluble ILT2 and ILT4 act as CD8-antagonists that inhibit effector CD8⁺ T cell priming by LCs, together with promoting the production of IL-4 and IL-10. The results presented herein indicate that ILT receptor family members can skew the polarization of CD8⁺ T cell responses and strategies to block ILT expression on dendritic cells (DCs) may be useful to augment dendritic cell function to enhance responses to cancer or chronic viral infections.