Role of co-stimulatory signal in long-term acceptance of human kidney allogrfts.

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To evaluate the role of co-stimulatory signal in long-term human kidney allograft acceptance, CD 2, CD 11a and CD 28 expression on peripheral lymphocytes of human kidney transplant patients were examined in 67 kidney transplant patients, 14 healthy volunteers and 10 hemodialysis patients. Only CD 28 was remarkably depressed in the kidney transplant patients, which was significantly correlated with the duration of graft survival. In age matched healthy volunteers and hemodialysis patients did not have depressed expression of co-stimulatory antigens. Depressed CD28 was induced mainly on CD4 positive T cells. The CD28-negative CD 4-positive T cell did not express CD 25, CD69, V alpha 24 nor CTLA-4. RT-PCR and southern blotting analysis for repertoire of the V beta chain indicated remarkable deviation in the CD28-negative CD 4-positive T cell. Also, it had elevated expression of INF-gammer and TGF-beta 1, but not IL-4 and IL-10. In MLC study between kidney transplant patients, donors and third party, donor specific suppression was observed in patients with the more CD28-negative CD 4-positive T cells. In prospective 3 year-survey of the rate of CD28-negative CD 4-positive T cell/CD 4-positive T cell in 74 long-term kidney transplant patients, it was lower in the recipients with chronic rejection.In conclusion, the CD28-negative CD 4-positive T cell might be induced by continuous stimulation of donor antigens and might play a significant role in suppression of rejection.