CD28-CD80/CD86 interactions in testicular immunoregulation.

The expression of two accessory molecules on antigen-presenting cells (APC), the CD80/ B7-1 and CD86/B7-2 antigens, was studied in the testis of normal and non-obese diabetic (NOD) mice. In addition, the effect of CD28 stimulation on suppression of lymphocytes by testicular products was investigated. The testes of 4-week old NOD mice or normal BALB/c mice and the testis of 17-21-week old BALB/c mice contained no CD80 or CD86 expressing cells. In contrast, CD80+ and CD86+ cells were present in the testis of 14-22-week old NOD mice. The CD80+ cells and most of the CD86+ cells were CD11b/CD18 negative. There were some CD11b/CD18+ cells that expressed CD86 weakly. The CD80+ and CD86+ cells were often located adjacent to the vessel walls where a leukocyte not expressing CD80 or CD86 had attached to the endothelium. Some CD80+ and CD86+ cells were present among the interstitial cells. The CD80 and CD86 antigens could not be observed in the same cells as judged from stainings in parallel sections. Stimulation of ConA- or anti-CD3 epsilon-primed peripheral blood or spleen lymphocytes with anti-CD28 was able significantly to antagonize the growth-inhibitory effect of the M(r) > 5 K fraction of testis extracts, but could not abolish it with increasing concentrations of testis extract. The results suggest that T lymphocytes can not be activated locally in the testis of BALB/c and young NOD mice because of the absence of the necessary CD28 ligands, CD80 and CD86, from the APCs and because of the suppression of T lymphocytes by the testicular products. In the testis of older diabetic NOD mice lymphocyte activation may occur because the testes of these mice contain CD80+; CD11b/CD18-, CD86+; CD11b/CD18+ and CD86+; CD11b/CD18- cells and therefore, CD28 co-stimulation, which can antagonize the suppressive effect of testis extract, may occur. The possibilities for clonal anergy in testicular immunoregulation are discussed.