Regulatory mechanism of delayed-type hypersensitivity in mice. V. Augmentor cells for DTH responses.

Abstract

Mice primed with 1 microgram of reduced and alkylated ovalbumin (RA-OA) developed not only long-lived memory cells for delayed-type hypersensitivity (DTH), capable of differentiating into DTH-effector T cells (DTH-Te) against ovalbumin (OA) when restimulated in vitro with OA, but also spleen cells capable of augmenting recipients' DTH responses to OA when transferred into cyclophosphamide (CY)-pretreated mice. The augmenting activity in spleen cells, upon transfer, was found 7 days, but not 21 or 91 days, after priming with RA-OA, although memory DTH-Te were present throughout the period of observation. The loss of augmenting activity after day 7 of priming was not due to the presence of suppressor cells; spleen cells taken 21 days after priming failed to suppress, upon transfer, the augmenting activity in 7-day-primed spleen cells as well as induction and expression of DTH responses to OA. When 7-day-primed spleen cells were fractionated on a discontinuous bovine serum albumin density gradient, the augmenting activity was found only in the medium-density-cell layer, although memory DTH-Te were separated in the high-density layer. Augmentation of DTH-Te generation could also be demonstrated in vitro when 7-day-primed spleen cells, but not 21-day-primed spleen cells, were added to cultures of spleen cells from CY-pretreated mice. These results indicate that, in the 7-day-primed spleen, there is an augmentor cell population which is different from memory DTH-Te and interacts with CY-resistant unprimed cells to facilitate DTH-Te generation.