Unique Identifier : AIDSLINE MED/20243542
Costimulation of T cell activation involves both the B7:CD28 as well as
the CD40 ligand (CD40L):CD40 pathway. To determine the importance of
these pathways to in vitro and in vivo T cell activation, a direct
comparison was made of the responses of TCR transgenic T cells lacking
either CD28 or CD40L. In vitro, CD28-/- T cells showed a greater
reduction in proliferative responses to Ag than did CD40L-/- T cells.
The absence of CD28 resulted in defective Th2 responses, whereas
CD40L-/- T cells were defective in Th1 development. In vivo, CD28-/- T
cells failed to expand upon immunization, whereas CD40L-/- T cells could
not sustain a response. These results suggest that CD28 is critical for
initiating T cell responses, whereas CD40L is required for sustained Th1
responses. The different functional roles of these costimulatory
pathways may explain why blocking B7:CD28 and CD40L:CD40 interactions
has an additive effect in inhibiting T cell responses.
JOURNAL ARTICLE Adoptive Transfer Animal Antigens,
CD28/GENETICS/*PHYSIOLOGY Antigens, CD40/*METABOLISM Cell
Differentiation/IMMUNOLOGY Cells, Cultured *Immune Tolerance/GENETICS
Ligands *Lymphocyte Transformation/GENETICS Membrane
Glycoproteins/DEFICIENCY/GENETICS/*PHYSIOLOGY Mice Mice, Inbred BALB C
Mice, Knockout Mice, Transgenic Support, U.S. Gov't, P.H.S.
Cells/CYTOLOGY/IMMUNOLOGY Th2 Cells/CYTOLOGY/IMMUNOLOGY