Nature of APCs for MLRs

For sensitized T cells responding to MHC alloanti-gens, a number of different cell types such as macrophages (M<J>s), dendritic cells (DCs) and B cells express APC function. Which of these cell types have APC function for unprimed T cells is controversial. One school of thought holds that unprimed T cells can be stimulated by only one type of cell, namely DCs. Others argue that, although DCs do express extremely potent APC function for unprimed T cells, significant APC function can also be provided by M<|)s and B cells. For CD8 + cells, some workers (this writer) maintain that many different cell types, including various class II-negative cells, can express potent APC function for MHC alloantigens. Others refute this view and attest that only DCs can stimulate CD84 cells.

The resolution to the issue of which particular cell types express APC function for unprimed T cells is likely to hinge on defining the precise signals required for T cell activation. In this respect, it is now well established that primary T proliferative responses require costimulatory signals delivered through T cell contact with molecules such as B7 (B7-1, B7-2) and ICAM-1 on APCs; these molecules are expressed at a particularly high level on DCs. Costimulation boosts signaling via the TCR and is crucial for the production of growth factors such as IL-2. Although costimulation is probably important for all primary responses, recent work suggests that the requirement for costimulation is less stringent for high-affinity T cells than for low-affinity cells. This could explain the different findings on the role of DCs in MLRs. Thus, with their high expression of costimulatory molecules, DCs could be crucial for stimulating T cells with low-to-average affinity for antigen, whereas other cell types could be sufficient for stimulating high-affinity T cells.

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