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The Roles of CD28 and CD40 Ligand in T Cell Activation and Tolerance

2000; American Association of Immunologists; Volume: 164; Issue: 9 Linguagem: Inglês

10.4049/jimmunol.164.9.4465

1550-6606

Kimberly C. Howland, Lara J. Ausubel, Cheryl A. London, Abul K. Abbas,

Immune Cell Function and Interaction

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.