Delayed cutaneous hypersensitivity in normals: choice of antigens and comparison to in vitro assays of cell-mediated immunity.

In 81 normal subjects, ages 19 to 100 yr (mean 52), we studied the prevalence of positive 48 hr skin reactions to six antigens: fluid tetanus toxoid, Candida albicans, SK/SD, Trichophyton, PPD, and coccidioidin. Of these, C. albicans was most frequently reactive (92%); SK/SD (51%) and tetanus (49%) were less so. Each of the remaining three antigens was reactive in less than 42% of the subjects. The minimum number of antigens required to detect delayed hypersensitivity in 100% of subjects was two: C. albicans and tetanus. We found no correlation between skin reactivity at 20 min, 6 hr, and 48 hr for most of the antigens studied, suggesting different mechanisms for reactions occurring at each time. In 60 of the subjects, lymphocyte stimulation index (LSI) with tetanus toxoid and monocyte chemotaxis (MC) assays were done. The natural log of the area of induration at 48 hr after tetanus skin testing (I48) increased as a function of LSI (p less than 0.005) and MC (p less than 0.025) by multiple regression analysis. Skin testing was less sensitive than LSI as a test for cell-mediated immunity in our population. However, because of availability and correlation with LSI, delayed cutaneous hypersensitivity should be tested initially. For this purpose, tetanus toxoid appears to be a useful antigen when used in combination with C. albicans.