Dendritic cells in the human vaginal mucosa can direct CD4+ T cell responses by expressing surface OX40L.

INTRODUCTION

Immunity in the vaginal mucosa (VM) is of critical importance for the protection from infections and cancers. Dendritic cells (DCs) are the major antigen-presenting cells that can induce and control T cell responses. Interestingly, VM Langerhans cells (vLCs) and VM CD1c+CD14- DCs (vDCs) polarize CD4+ T cells toward Th2-type. However, the mechanisms underlying Th2 polarization by vDCs remain unknown.

METHODS

OX40L expression was determined in the human VM tissue sections, followed by the measurement of OX40L expression on vLCs, CD1c+CD14- vDCs, and VM macrophages (vMØs) by flow cytometry. The roles of OX40L on vDC subsets in the induction of different types of CD4+ T cell responses were assessed.

RESULTS

Both vLCs and CD1c+CD14- vDCs express surface OX40L. Neutralizing OX40L with anti-OX40L antibody significantly decreased the frequency of Th2-type CD4+ T cells with a reduction of CD4+ T cell proliferation, while increasing the frequency of IL - 10-producing CD4+ T cell responses. Anti-OX40L did not affect vLC- or CD1c+CD14- vDC-induced Th1-type T cell responses. OX40L also contributed to the induction of IL - 21+CD4+ T cell responses by vLCs and CD1c+CD14- vDCs. In contrast to vLCs and CD1c+CD14- vDCs, vMØs expressed a minimal level of surface OX40L. Likewise, anti-OX40L did not significantly affect vMØ-induced CD4+ T cell responses.

CONCLUSIONS

OX40L contributes to vLC- and CD1c+CD14- vDC-induced Th2 polarization. It also significantly affects the frequency of vLC- and CD1c+CD14- vDC-induced IL - 10+ and IL - 21+CD4+ T cells. This study provides new insights into the immunological landscape of the human VM tissues, with implications for the development of targeted immunomodulatory strategies at this mucosal site.