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Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):265-73.

Costimulation of T cells by OX40, 4-1BB, and CD27.

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Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.


Costimulatory signals have been defined as signals brought about by ligation of membrane bound molecules that synergize with, or modify, signals provided when the T cell receptor engages peptide-MHC complexes. In large part, costimulatory signals are essential for many facets of a T cell response, and the general rule is that without these signals, a T cell is ineffective and may often succumb to death or become unresponsive. Until recently, costimulation has been dominated by studies of the Ig superfamily member, CD28, a constitutively expressed molecule that is required to initiate a majority of T cell responses. However, growing evidence over the past few years has now shown that several members of the TNFR family, OX40 (CD134), 4-1BB (CD137), and CD27, are equally important to the effective generation of many types of T cell response. In contrast to CD28, these molecules are either induced or highly upregulated on the T cell surface a number of hours or days after recognition of antigen, and appear to provide signals to allow continued cell division initially regulated by CD28 and/or to prevent excessive cell death several days into the response. An argument can be made that these molecules control the absolute number of effector T cells that are generated at the peak of the immune response and dictate the frequency of memory T cells that subsequently develop. The exact relationship between OX40, 4-1BB, and CD27, is at present unknown, including whether these molecules act together, or sequentially, or control differing types of T cell response. This review will focus on recent studies of these molecules and discuss their implications.

[Indexed for MEDLINE]

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