Isoforms of the CD45 common leukocyte antigen family: Markers for human T-cell differentiation

Abstract

The diverse host defense and immunoregulatory functions of human T cells are performed by phenotypically heterogeneous subpopulations. Among the membrane antigens that are differentially expressed by reciprocal human T-cell subsets are the CD45RA and CD45RO isoforms of the common leukocyte antigen family, which have been hypothesized to identify "naive" and "memory" T cells, respectively. The CD45RA antigen is first expressed by T-lineage cells relatively late during their intrathymic maturation and continues to be expressed by most T cells in the immunologically naive neonate. With increasing age and antigenic exposure, however, CD45RA-/RO+ cells become more prevalent in the circulation and comprise the majority of cells in tissues. Analyses of the functional capabilities of CD4+CD45RA+ and CD4+CD45RO+ cells have shown that proliferative responses to "memory" recall antigens or the ability to provide help for antibody production are functions uniquely performed by CD4+CD45RA-/RO+ cells. The major immunoregulatory functions described for CD4+CD45RA+ cells involve suppression of immune responses, either directly or via the induction of suppressor activity by CD8+ cells. Two general models of differentiation have been proposed to describe the lineal relationship of these T-cell subsets. Although these subsets could represent mature, phenotypically and functionally stable progeny arising from separate differentiation pathways, there is considerable experimental support for the hypothesis that CD45RA-/RO+ cells are "memory" cells that derive from "naive" or "virgin" CD45RA+/RO- precursors via an activation-dependent postthymic differentiation pathway. Altered frequencies of CD45RA+ and CD45RO+ T cells have been observed in a variety of different clinical conditions, particularly diseases manifesting altered immune function. These findings have contributed new information concerning the physiological events regulating the in vivo generation of these T-cell subsets. In addition, they may provide clues to the pathogenetic processes associated with certain diseases.

CD8αα memory effector T cells descend directly from clonally expanded CD8α+βhigh TCRαβ T cells in vivo

“…Neonatal T cells are exclusively composed of naive cells, and in repeated antigenic stimulations with age, infection and autoreactivity convert the naive cells to effector and memory cells. 32 Therefore, CD8␣␣ and CD8␣ ϩ ␤ low ␣␤ T cells may represent antigen-experienced cells. A wide range of the variation in the frequencies of these cells among adult individuals supports this notion.…”

Immunoarchitecture of lymphoid tissue in HIV-infection during antiretroviral therapy correlates with viral persistence

“…27 These cells, immunologically naive, turn into a CD45RO þ phenotype characteristic of memory T cells, after challenging an antigen in the periphery. 28 The balance between the naive and memory T cells is crucial for maintaining an efficient immune response. In HIV infection, naive and memory CD4 þ T-cell counts decrease in different stages of disease.…”

Altered representation of naive and memory CD8 T cell subsets in HIV-infected children.

“…In particular, the subset that expresses the CD45RA surface marker (CD45RAhi), which is often referred to as the naive (or virgin) subset, makes a relatively poor cytokine response after T cell receptor stimulation. In contrast, the so-called memory subset, which secretes a wide variety of cytokines in response to T cell receptor stimulation, expresses CD45RO (another isoform of CD45 [reference 3]) instead of CD45RA (3,4).…”