The granule exocytosis pathway of cytotoxic lymphocytes (Tc and NK cells) is critical for control of tumor development and viral infections. Granule-associated perforin and granzymes are key components in Tc cell-mediated function(s). On the basis of studies that showed granzymes A, B, C, K and M, to induce apoptosis in vitro, all granzymes were thought to also induce cell death in vivo. This review summarizes our present understanding of the biological processes elicited by purified granzyme A and granzyme as well as the processes induced by the more physiologically relevant cytotoxic cells secreting these proteases. The combined evidence supports the concept that the granule secretion pathway is not mono-specific but rather poly-functional including induction of pro-inflammatory cytokines, besides their widely appreciated apoptotic properties.

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The idiotopic repertoire expressed by antigen-specific suppressor T cells (Ts) generated by Streptococcus pneumoniae strain R36a (Pn) in BALB/c strain mice was investigated using a panel of five monoclonal anti-idiotopic antibodies against TEPC-15/HOPC-8 myeloma proteins. Previous studies suggested that the anti-idiotopic antibodies recognize distinct idiotopic determinants within the T15 idiotype, and that Pn-reactive B cells express all of those idiotopes as shown by a specific inhibitory effect of the anti-idiotopic antibodies on induction of anti-Pn response in vitro as well as on the mature antibody plaque-forming cells. In this study we asked the question of whether anti-idiotopic (Id) can block the inductive and/or effector phases of generation of Ts which act on the Pn-reactive B cells. The presence of anti-Id during the activation of T cells with Pn did not prevent the generation of Ts. However, suppression mediated by Ts on responder lymphocytes (cultures of spleen cells or B cels) was inhibited (reversed) by four out of five anti-Id. Some of the antibodies recognize hapten (phosphorylcholine)-inhibitable Id in the paratope of Ig whereas others are directed against nonparatopic Id. These data indicate that the antigen receptor on Ts includes VH sequences both within and without the immunoglobulin in paratope, and that the Id repertoir of Ts overlaps with that of B cells.

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