ＢＣＧによる免疫応答の制御

We observed that delayed-type hypersensitivity (DTH), which was estimated byfootpad reactions in mice immunized with Bacillus Calmette Guerin (BCG) cell walls (CW), was suppressed by previous injection of live BCG. We analysed the DTH suppression usingmacrophge migration inhibition (MI) test. Peritoneal exudate cells (PEC) from live BCG-injected mice (L-BCG-PEC) were mixed with PEC from BCG-CW immunized mice (Effector PEC). As a control, we used normal mouse PEC (N-PEC). MI activity ofmixture of Effector PEC and N-PEC was observed, but not of Effector PEC and L-BCGPEC. The result showed that suppressor cells in L-BCG-PEC suppressed the MI activity of the Effector PEC. The characteristics of the suppressor cells in L-BCG-PEC were asfollows:<BR>1. The suppressor cells in L-BCG-PEC belonged to macrophage.<BR>2. The suppressor macrophages were induced in PEC at least 12 days after live BCG injection.<BR>3. The suppression was antigen non-specific and operated across the H-2 barrier.<BR>4. Prostaglandin E1 produced by the suppressor macrophages suppressed the MI activityof the Effector PEC.<BR>5. The suppressor macrophages were sensitive to methotrexate (MTX).<BR>6. MTX-sensitive cells in nomal mouse bone marrow (Natural suppressor cells) suppressed the MI activity of the Effector PEC. The natural suppressor cells werecharacterized by immature macrophages. No the suppressor macrophages against MI activity were induced by live BCG injection in PEC of MTX-treated mice.<BR>Naturalsuppressor cells in normal mouse bone marrow may be of origin of the suppressor macrophages.<BR>On the other hand, we also observed that BCG-CW induced DTH response wassuppressed in killed BCG-injected mice and that the MI activity of mixture of the Effector PEC and the PEC from mice injected intravenously with killed BCG (K-BCG-PEC) waspositive.<BR>This finding suggested that no in vivo phenomenon (DTH) corrlated in vitrophenomenon (MI activity of PEC) and that no suppressor cells were induced in K-BCGPEC.<BR>To analyze the mechanisumus of DTH suppression in killed BCG injected mice, weexamined the spleen cells from mice injected with killed BCG (K-BCG-sp-cells).<BR>The MIactivity of mixture of K-BCG-sp-cells and the Effector PEC was negative, suggestingthat suppressor cells in the K-BCG-sp-cells suppressed the MI activity of the Effector PEC.<BR>The characteristics of the suppressor cells in K-BCG-sp-cells were as follows:<BR>1. The suppressor cells in K-BCG-sp-cells were Ly-2+, I-J+ cells.<BR>2. The suppressor T cells were sensitive to cyclophosphamide.<BR>3. The suppressor T cells operated antigen-nonspecifically.<BR>4. DTH was suppressed in mice treated with tuberculin active peptide (TAP), theantigen portion of BCG, and muramyl dipeptide (MDP), the adjuvant portion of BCG. TAP and MDP induced antigen specific suppressor T cells and antigen nonspecificsuppressor T cells, respectively.<BR>Therefore, two different kinds of suppressor T cells which were induced by antigen and adjuvant of BCG may operate in killed BCGinduced DTH suppression.