Antigen‐specific helper T cells are essential for cytotoxic T cell responses to metabolically inactivated stimulator cells

摘要

AbstractPrimed spleen cells respond well to metabolically inactivated stimulator cells while normal spleen cells do not. This observation has been interpreted as showing that cytotoxic T cell precursors are different from unprimed precursors in their antigen recognition requirements for induction. A different model is proposed here which accounts for these observations as due to enhanced helper cell levels in primed populations. Experiments are described in this study which test several predictions of this model. These experiments show that in the presence ofin vitroprimed helper T cells, normal cells are able to respond efficiently to glutaraldehyde‐fixed stimulator cells. The helper effect is antigen‐specific. Since unprimed spleen cells can be efficiently induced by metabolically active stimulators (γ‐irradiated cells) and can respond to glutaraldehyde‐fixed antigen (metabolically inactive cells) only in the presence of specific helper cells, it seems reasonable to propose that helper cell signals are enhanced by a nonantigenic property of γ‐irradiated stimulator cells requiring metabolic activity. It is also clear that glutaraldehyde‐fixed cells are anti‐ genically intact as helper cells, primed to antigens on γ‐irradiated stimulator cells, efficiently and specifically help a response to fixed stimulators. Conversely, helper cells primedin vitroto glutaraldehyde‐fixed stimulators recognize antigen on γ‐irradiated stimulator cells. The level of help generated in response to glutaraldehyde‐ fixed stimulator cells is at least 10‐fold higher in primed cells than in normal cells. In addition, primed spleen cells can be inducedin vitroto yield helper function by both fixed or unfixed stimulator cells. Normal helper cell precursors are induced at least 100‐fold more efficiently by γ‐irradiated as compared to glutaraldehyde‐fixed stimulator cells. This work supports the idea that a major effect of priming, which allows primed cells to respond to metabolically inactive stimulators, is to enhance levels of helpe