Cord blood T lymphocytes lack constitutive perforin expression in contrast to adult peripheral blood T lymphocytes

Abstract

Perforin is the cytolytic pore-forming protein, which alone can be responsible for the lethal hit in one of the killing mechanisms used by natural killer (NK) cells or cytotoxic T lymphocytes. In this study, perforin expression was investigated in cord blood (CB) lymphocytes to determine their killing potential in vivo. The majority of CB CD3- NK cells had the protein. Compared with adult perforin-positive NK cells, a significantly lower percentage of cells expressing CD56 and CD57, the related neural cell adhesion molecules, was found (P = .0001). Perforin was also present in a unique immature CB NK-cell subset, characterized by cytoplasmic CD3 antigen (Ag) expression. In CB, very few CD8 perforin-positive T lymphocytes could be detected, but they were in significant numbers in adult peripheral blood (P = .02). A substantial proportion of these cells (70% +/- 23%) lacked the CD28 T-cell coactivation Ag, and they were able to exert NK-like, major histocompatibility complex nonrestricted cytolytic activity. CD4+ and gamma delta-T cells expressing perforin were absent from CB, but low numbers of such cells were detected in adult peripheral blood (P = .0001). Therefore, the spontaneous cytolytic activity of CB lymphocytes appeared to be dependent on well-represented perforin-positive NK cells, which were shown to efficiently lyse NK-sensitive target cells.

Differing activation status and immune effector molecule expression profiles of neonatal and maternal lymphocytes in an African population

“…Berthou and colleagues found no constitutive expression of perforin in cord blood cd or CD4 + T cells as opposed to adult blood cells, whereas cord blood CD8 + T cells expressed perforin. 25 We therefore conclude that the perforin expressing CD3 + T cells we detected here belong to the CD8 + T cell subset.…”

“…Perforin and granzyme B are important effector molecules of cytotoxic T and NK cells that mediate target cell lysis and induction of apoptosis. 25 Expression of these molecules was examined both ex vivo and after non-specific stimulation. Maternal cd and CD3 + T cells expressed both perforin and granzyme B ex vivo but expression by cord cd or CD3 + T cells was minimal (Table 1).…”

“…28 Other studies have reported neonatal NK cell cytotoxicity to be low 6,25,29 but capable of being enhanced in the presence of exogenous IL-2 24 and to reach levels comparable to adults upon addition of IL-12. 6,25 We found that, following stimulation, lower proportions of CBMC expressed cytokines of both the Th1 and Th2 types compared with maternal PBMC, a finding that we assume to be an indication of their decreased functional capacity. This observation is broadly in accordance with other studies of neonatal and adult cells in non-African populations 2,6-8 although it should be noted that comparability is hampered somewhat by the varying methods of stimulation used in these different studies.…”

Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood

“…The immaturity of lymphocytes in CB probably reduces the risk and severity of GVHD [11][12][13][14]. One study has shown that the cytotoxic activity in MLR of CB T cells was minimal [15].…”

Complementary and contrasting roles of NK cells and T cells in pediatric umbilical cord blood transplantation

“…The overwhelming majority of T lymphocytes present in UCB is naïve, shows little baseline cytotoxicity, and exhibits atypical functional properties. Indeed, the T lymphocytes secrete lower levels of IL-2, IL-4, IL-10, and IFN-␥ in vitro and express lower levels of Gr and perforin, molecules that are hallmarks of T H 1 responses [112,113]. Based on their production of high levels of IL-13, UCB T cells also exhibit an antiinflammatory T H 2/Tc2 bias [114].…”