Time course and histological differences between sheep red blood cells and tuberculin DTH reactions in mice

Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/mouse) or with attenuated viable Mycobacterium bovis (4 X 10(6) BCG/mouse) inoculated subcutaneously and elicited, respectively, with SRBC or protein-purified derivative (PPD), were studied regularly in separate groups of outbred mice and compared during a period of one year following immunization. The present report shows the existence of two distinct types of DTH reactions. The SRBC type consists of a reaction which peaks consistently at 18 h, reaches a maximum 4 days after immunization, and decreases progressively until the fourth month. This local reaction, mediated by specific committed T cells as demonstrated by adoptive transfer experiments, was shown to consist mainly of a polymorphonuclear leukocyte infiltration. The PPD type consists of a local reaction which presents a different time course, the peak shifting from 18 to 42 h during the first two months after immunization, and which persists unchanged over a year after immunization. This second type of DTH reaction consisted of an early phase of polymorphonuclear infiltration followed by an increased number of mononuclear cells. Evidence is also given that the differences in the expression of these two types of DTH reactions depended neither upon the physical characteristics of the two antigens used for elicitation nor upon the nonspecific environmental modulating activity of BCG, since soluble SRBC protein and heat-killed BCG cells elicited the same distinct types, and the two distinct DTH reaction types could be elicited in mice immunized with both BCG and SRBC.