Expression of perforin and cytolytic potential of human peripheral blood lymphocyte subpopulations

Abstract

To verify the physiological role of the pore-forming protein perforin in vivo, its expression in subpopulations of human peripheral blood lymphocytes was examined by immunocytochemical staining and their cytolytic potentials compared. In addition to NK cells and gamma delta T cells, which uniformly expressed abundant perforin in their cytoplasmic granules, only a small subpopulation of CD8+ alpha beta T cells contained perforin, namely the CD11b+ subset. However, in vitro activation with an anti-CD3 antibody and IL-2 induced perforin expression in approximately 50% of the CD8+CD11b- T cells and also in a small subset of CD4+ T cells. A distribution of perforin in CD8+ and CD4+ T cells, similar to in vitro activated T cells, was observed in fresh peripheral blood lymphocytes from infectious mononucleosis patients. In all instances, the expression of perforin correlated with the cytolytic potential of these subpopulations. The results strongly suggest that perforin plays a role in the manifestation of cytotoxic activity in vivo.

A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

“…In NK cells, Ksp37 is exclusively expressed in the CD56 dim CD16 bright population, which has the highest cytotoxic potential among NK cells (34). In CD8 ϩ T cells, surface phenotype (CD27 Ϫ CD11b ϩ ) and cytokine profile (IFN-␥ high IL-4 low IL-2 low ) of Ksp37-expressing cells well conform to the criteria for the effector CD8 ϩ T cell subset that has the highest cytotoxic ability among CD8 ϩ T cells (26,27). A recent report that CD56 expression can define the cytotoxic effector subset among CD8 ϩ T cells (35) is also consistent with this notion, because most Ksp37-expressing T cells also expressed CD56 (data not shown).…”

“…Circulating CD8 ϩ T cells can be classified into three major subsets based on the expression of CD45RA and CD27 Ags: CD45RA ϩ CD27 ϩ naive, CD45RA Ϫ CD27 ϩ memory, and CD45RA ϩ CD27 Ϫ effector subsets (26). Effector CD8 ϩ T cells, which have the highest cytotoxic activity among these subsets, highly express integrins such as CD11b and produce a large amount of IFN-␥ but little, if any, IL-2 (26,27). CD45RA Ϫ CD27 Ϫ CD8 ϩ T cells, which form a minor population among circulating CD8 ϩ T cells, also possess the properties similar to the effector subset (26).…”

“…We further investigated Ksp37-expressing lymphocytes for expression levels of perforin, a pivotal molecule in granule-mediated cytotoxicity (27,28). In adult PBMCs, Ksp37 expression was associated with the expression of perforin in CD16 ϩ NK cells, CD8 ϩ T cells, ␥␦ T cells, and CD4 ϩ T cells, although expression levels of perforin in CD4 ϩ T cells were lower than those in the other three cell types (Fig.…”

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

“…The CD28 ÿ T cell subset is mostly correspondent to the CD11b or CD57 T cell subset in normal PBMC [14,15]. Increased CD57 or CD11b T cell subset in PBMC has been reported after BMT [21] or in the course of infection by cytomegalovirus [22] and Epstein-Barr virus (EBV) [23]. Recently, an increased proportion of CD28 ÿ T cells was also reported in HIV infection [39][40][41].…”

“…All these data indicate that CD28 -T cells may possess distinct functional roles from CD28 + T cells in an immune response. The increase of this population has been reported in certain clinical situations, such as after BMT [21] or in the course of viral infections [22,23]. It seems that abnormal T cell activation by allo-antigens or viral antigens might be associated with such clinical situations in vivo.…”