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The roles of CD28 and CD40 ligand in T cell activation and tolerance.
Howland KC; Ausubel LJ; London CA; Abbas AK; Immunology Research
July 30, 2000
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. T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY/*METABOLISM/TRANSPLANTATION Th1 Cells/CYTOLOGY/IMMUNOLOGY Th2 Cells/CYTOLOGY/IMMUNOLOGY