A novel subpopulation of CD45RA⁺ CD4⁺ T cells expressing IL-2 receptor α-chain (CD25) and having a functionally transitional nature into memory cells

Abstract

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.

A Role for TGF-β in the Generation and Expansion of CD4+CD25+ Regulatory T Cells from Human Peripheral Blood

“…ϩ CD25 ϩ -regulatory T cells described by others (3)(4)(5)(6)(7)(8)33). Moreover, we have shown that CD4reg block CD8 ϩ T cells from responding to alloantigens and that this effect is only partially reversed by exogenous IL-2.…”

“…One regulatory subset that has been well characterized expresses cell surface IL-2R ␣-chains (3,4). These CD4 ϩ CD25 ϩ T cells differentiate in the thymus and are exported to the periphery, where they suppress the activation of potentially self-reactive cells (3)(4)(5)(6)(7)(8). Injection of peripheral T cells from normal mice depleted of CD4 ϩ CD25 ϩ T cells into athymic mice results in a high incidence of organ-specific autoimmune disease (3,4).…”

Functional Maturation of CD4+CD25+CTLA4+CD45RA+ T Regulatory Cells in Human Neonatal T Cell Responses to Environmental Antigens/Allergens

“…The lack of CD45RO expression has been described by all groups who have examined the phenotype of these cells in cord blood (34,37,39) and suggests that cord blood CD4 ϩ CD25 ϩ regulatory T cells are a naive (CD45RO Ϫ CD45RA ϩ ) population, contrasting with the memory (CD45RO ϩ CD45RA Ϫ ) population found in peripheral blood from adults. Similarly, far fewer cord than adult blood CD4 ϩ CD25 ϩ T cells express glutathione transferase (40).…”

Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals

“…Low IgG and IgA concentrations during infancy are partly explained by the deficient helper functions of CD4^ T cells in vivo. Namely, CD4'*" T cells from neonates and infants are predominantly CD45RA^ naive T cells and produce few ofthe cytokines required for production of IgG and IgA [12,24]. Our culture system provided these signals by adding CD62Lm emory CD4"^ T cells to PWM-stimulated cultures.…”

“…major cause of immune dysfunction during this period [7][8][9]. Neonatal T cells are unable to induce effective immunoglobulin class switch in B cells, because they virtually lack the CD45RO'*' (memory) subpopulation of 004"^ T cells [10][11][12]. In addition, neonatal B cells themselves are immature and produce only low levels of immunoglobulin even when the cells are stimulated by T-independent stimuli, such as Staphylococcus aureus Cowan I (SAC) and IL-2 [13].…”