Cutaneous immunization rapidly activates liver invariant Vα14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity

RA Campos, M Szczepanik, A Itakura… - The Journal of …, 2003 - rupress.org
RA Campos, M Szczepanik, A Itakura, M Akahira-Azuma, S Sidobre, M Kronenberg
The Journal of experimental medicine, 2003rupress.org
T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated
by B-1 cells that produce IgM, which activates complement to promote T cell passage into
the tissues. We now show that Vα14i NKT cells induce B-1 cell activation likely by releasing
IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/−
NKT cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT cells.
Transfers are not effective if cells are derived from IL-4−/− mice. Staining with specific …
T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 cells that produce IgM, which activates complement to promote T cell passage into the tissues. We now show that Vα14i NKT cells induce B-1 cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT cells. Transfers are not effective if cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 cells also reconstitutes CS responses in NKT cell–deficient mice. The B-1 cells act downstream of the Vα14i NKT cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT cells are stimulated to produce IL-4, which activates B-1 cells to produce Ag-specific IgM, subsequently needed to recruit effector T cells for elicitation of CS responses.
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