Stout R D, Bottomly K
Department of Microbiology, College of Medicine, East Tennessee State University, Johnson City 37614.
J Immunol. 1989 Feb 1;142(3):760-5.
IFN-gamma-producing (TH1) and IL-4-producing (TH2) clones were assayed for their ability to directly induce cytostatic activity in macrophages generated from splenic myeloid precursors (M phi-c). In the presence, but not in the absence, of antigen, TH1 clones activated the M phi-c to inhibit the growth of P815 tumor cells in vitro. TH2 clones were not able to activate such effector activity in the M phi-c. The M phi-c did effectively present Ag to the TH2 clones as evidenced by the proliferation of TH2 cells cultured with Ag in the presence, but not in the absence, of M phi-c. Therefore, although both TH1 and TH2 were activated by cognate interaction with antigen presenting M phi-c, only TH1:M phi-c interactions displayed reciprocity resulting in activation of the M phi-c. TH1-derived lymphokines or rIFN-gamma, in the presence of LPS, could activate proteose-peptone elicited M phi, resident peritoneal M phi, and M phi-c whereas neither TH2-derived lymphokines nor rIL4 could induce detectable activity in any of the 3 M phi populations. IFN-gamma, in the absence of LPS, could activate the elicited M phi and to a lesser and more variable degree, the resident M phi Only the M phi-c consistently required both IFN-gamma and LPS for induction of cytostatic activity. Since M phi-c consistently required at least two signals for activation, the ability of TH1-derived lymphokines to synergize with TH2 cells in M phi activation was examined. TH2 could activate the Ag-presenting M phi-c in the presence of IFN-gamma. The ability of added IFN-gamma to synergize with TH2 indicates that the cognate interaction between TH2 and antigen presenting M phi-c does result in delivery of at least one of the signal required for M phi activation.
检测产生干扰素-γ（TH1）和产生白细胞介素-4（TH2）的克隆，以评估它们直接诱导由脾髓系前体细胞产生的巨噬细胞（M phi-c）产生细胞抑制活性的能力。在有抗原存在而非无抗原存在的情况下，TH1克隆激活M phi-c以在体外抑制P815肿瘤细胞的生长。TH2克隆无法在M phi-c中激活这种效应活性。M phi-c确实能有效地将抗原呈递给TH2克隆，这可通过在有M phi-c存在而非无M phi-c存在的情况下，用抗原培养的TH2细胞的增殖来证明。因此，尽管TH1和TH2都通过与呈递抗原的M phi-c的同源相互作用而被激活，但只有TH1:M phi-c相互作用表现出互惠性，从而导致M phi-c的激活。在脂多糖（LPS）存在的情况下，TH1来源的淋巴因子或重组干扰素-γ可激活蛋白胨诱导的巨噬细胞、驻留腹膜巨噬细胞和M phi-c，而TH2来源的淋巴因子或重组白细胞介素-4在这三种巨噬细胞群体中均无法诱导可检测到的活性。在无LPS的情况下，干扰素-γ可激活诱导的巨噬细胞，并在较小且更具变异性的程度上激活驻留巨噬细胞。只有M phi-c始终需要干扰素-γ和LPS两者才能诱导细胞抑制活性。由于M phi-c始终需要至少两个信号才能激活，因此研究了TH1来源的淋巴因子与TH2细胞在巨噬细胞激活中协同作用的能力。在干扰素-γ存在的情况下，TH2可激活呈递抗原的M phi-c。添加的干扰素-γ与TH2协同作用的能力表明，TH2与呈递抗原的M phi-c之间的同源相互作用确实导致了巨噬细胞激活所需的至少一个信号的传递。
