Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity.
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 Valpha14i NKT cells induce B-1 cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jalpha18-/- and CD1d-/- NKT cell-deficient mice and is reconstituted by populations enriched for Valpha14i NKT cells. Transfers are not effective if cells are derived from IL-4-/- mice. Staining with specific tetramers directly showed that hepatic Valpha14i 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 Valpha14i NKT cells to restore CS initiation. In addition, IL-4 given systemically to Jalpha18-/- or CD1d-/- NKT cell-deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jalpha18-/- mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Valpha14i 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.
Campos
Regis A
RA
Department of Medicine, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520-8013, USA.
Szczepanik
Marian
M
Itakura
Atsuko
A
Akahira-Azuma
Moe
M
Sidobre
Stephane
S
Kronenberg
Mitchell
M
Askenase
Philip W
PW
D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000502:physiology*; D003877:Dermatitis, Contact / Q000209:etiology*; D005260:Female; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000502:physiology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D007075:Immunoglobulin M; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4