Histological and Immunopathological Studies of Delayed Hypersensitivity Reaction to Tuberculin in Mice

At 4 to 6 weeks after intravenous infection with 2 X 10(4) CFU of dispersed Mycobacterium bovis bacilli (BCG), C3H/HeNCrIBR and C57BL/6NCrIBR mice exhibited a strong reaction to purified protein derivatives, as evaluated by the increase in footpad swelling at both 24 and 48 h after local antigenic challenge. However, histological studies of the footpad skin demonstrated a prominent perivascular infiltration with polymorphonuclear cells at 6 and 24 h after purified protein derivative challenge, whereas mononuclear cells represented the majority of infiltrating cells only at 48 h. An immunopathological study of the footpad skin showed granular deposits of immunoglobulins and complement in vascular walls and perivascular tissues at 6 and 24 h. These results demonstrate that the footpad swelling observed 24 h after the antigenic challenge is caused by an Arthus-type reaction, whereas that caused by cell-mediated immunity appears at 48 h. Hence, delayed hypersensitivity must be evaluated at 48 and not 24 h after challenge.