The inhibitor of costimulation of T cells: abatacept.

Abstract

OBJECTIVE:

T cell costimulation is a key point in the regulation of immune tolerance, immune response, and autoimmunity. T cell activation does not take place upon the simple engagement of T cell receptor; a second signal is needed to fully stimulate T cells. There are a variety of molecules that can act as costimulators, and among those CD28/CD80 signaling plays a crucial role in modulating T cell response. Cytotoxic T lymphocyte antigen-4, CD152 (CTLA4) is a physiologic antagonist of CD28, and abatacept, a synthetic analog of CTLA4, has recently been approved to treat rheumatoid arthritis. An abnormal T cell activation is also believed to sustain psoriatic disease both at skin and joint sites. We aimed to evaluate the rationale of blocking CD28/CD80 signaling and the possible use of abatacept for treating psoriatic arthritis (PsA).

METHODS:

We reviewed the role of CD28/CD80 signaling in promoting T cell inflammation in psoriasis and the effects of CTLA4 modulation in experimental models of psoriasis and in humans.

RESULTS:

CD28/CD80 seems to be crucial in stimulating T cell activation and inflammation in psoriasis, and its inhibition by CTLA4 analogs or by anti-CD28 blocking antibodies is effective against psoriasis. Few data are available on abatacept, which seems to be valuable for the treatment of PsA but less useful in the therapy of skin psoriasis.

CONCLUSION:

Although the CD28 molecule is crucial in activating T cells and inflammation in psoriasis, data on the efficacy of abatacept in the treatment of PsA are still not conclusive.

• Authors: Florenzo Iannone, Giovanni Lapadula
• Journal: The Journal of rheumatology. Supplement (J Rheumatol Suppl) Vol. 89 Pg. 100-2 (Jul 2012) ISSN: 0380-0903 [Print] Canada
• PMID: 22751606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Inflammatory Agents
• B7-1 Antigen
• CD28 Antigens
• Immunoconjugates
• Abatacept

Topics

• Abatacept
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Arthritis, Psoriatic (drug therapy, immunology)
• B7-1 Antigen (metabolism)
• CD28 Antigens (metabolism)
• Humans
• Immunoconjugates (therapeutic use)
• Lymphocyte Activation (drug effects)
• Signal Transduction (drug effects)
• T-Lymphocytes (drug effects, immunology)
• Treatment Outcome