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 testi s of normal and non-obese diabetic (NOD) mice. In addition, the effect of CD28 stimulation on suppression of lymphocytes by testicular produ cts 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 p resent 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 CD1 1b/CD18 + cells that expressed CD86 weakly. The CD80 + and CD86 + cell s were often located adjacent to the vessel walls where a leukocyte no t 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 fr om stainings in parallel sections. Stimulation of ConA-or anti-CD3 eps ilon-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 inc reasing concentrations of testis extract. The results suggest that T l ymphocytes can not be activated locally in the testis of BALB/c and yo ung NOD mice because of the absence of the necessary CD28 ligands, CD8 0 and CD86, from the APCs and because of the suppression of T lymphocy tes by the testicular products. In the testis of older diabetic NOD mi ce lymphocyte activation may occur because the testes of these mice co ntain CD80 +, CD11b/CD18 -, CD86 +; CD11b/CD18 + and CD86 +; CD11b/CD1 8 - cells and therefore, CD28 co-stimulation. which can antagonize the suppressive effect of testis extract, may occur. The possibilities fo r clonal anergy in testicular immunoregulation are discussed.