The expansion of activated T cells, characterized by the expression of CD45RO as well as HLA-DR antigens, is a central feature in acute infectious mononucleosis (IM) induced by primary infection of Epstein- Barr virus (EBV). However, the fate of these activated T cells in this disease is not clearly understood. We found that, on simple culture, a large proportion of T cells isolated from acute IM patients died rapidly, but only a few T cells from normal individuals did. Morphologic observations and DNA fragmentation analysis showed that the loss of viability of IM T cells after incubation was mediated by apoptosis. IM T cells undergoing apoptosis resided exclusively in the CD45RO+ populations of both CD4+ and CD8+ T cells, most of which were shown to coexpress apoptosis-related Fas antigen. Some cytokines such as interleukin-2 (IL-2), IL-5, and IL-6 could rescue IM T cells from apoptotic cell death. The results seemed to imply that most of primed (CD45RO+) T cells in acute IM might be subject to apoptotic cell death, possibly when leaving from the local sites actively producing certain soluble factors required for their survival. Our studies suggest the programmed cell death of peripheral mature T cells as a mechanism of antigen-driven selection.

We studied two unrelated male probands with mild ornithine transcarbamylase (OTC) (E.C.2.1.3.3) deficiency presenting a similar clinical course. Previous analyses of their liver OTCs also revealed similar properties. To identify the underlying molecular defects, we first cloned the entire coding region of the OTC gene from one proband and found a single base-substitution (C to T) leading to the substitution of tryptophan for arginine at amino acid position 277. Using a genomic amplification technique followed by allele specific oligonucleotide hybridization, we identified the same point mutation in the OTC gene of the other proband. We observed the presence of the mutation among family members in at least three generations, and in one asymptomatic hemizygous sibling in each family.

Differential expression of various isoforms of leukocyte common antigen (CD45), which arises from alternate mRNA splicing, identifies naive and memory populations of human T cells. Some memory (CD45RO+ CD45RA-) populations of CD4+ T cells from adult individuals express IL-2 receptor (IL-2R) alpha-chain (CD25), but naive (CD45RO- CD45RA+) CD4+ T cells only do so to a small degree. We found that a small but significant fraction of CD4+ T cells in neonatal blood expressed CD25, although most generally exhibited the phenotype of naive cells. It was demonstrated that purified neonatal CD25+ CD4+ T cells expressed mRNA for the IL-2R alpha-chain. Two-color immunofluorescence analysis disclosed that a CD25+ population of neonatal CD4+ T cells had the naive (CD45RA+ CD45RO-) phenotypes. These CD25+ CD4+ T cells from newborns could express mRNA for some specified lymphokines such as IL-4, IL-5, and interferon-gamma on activation in a similar manner to CD45RO+ (memory) CD4+ T cells from adults. Notably, polymerase chain reaction analysis demonstrated that neonatal CD45RA+ CD4+ T cells expressing CD25 contained spliced mRNA transcripts possibly encoding CD45RO in addition to CD45RA-associated transcripts, seemingly indicating that this population might be in the recently antigen-primed states. Such a small population of CD45RA+ CD4+ T cells expressing CD25 appeared to be present in the blood throughout human life. The results suggest that CD4+ T cells with the naive (CD45RA+) phenotype expressing IL-2R alpha-chain (CD25) represent the novel transitional population in the maturation process of naive into memory CD4+ T cells.

No abstract