In vitro responses of human CD45R0^brightRA⁻ and CD45R0⁻RA^bright T cell subsets and their relationship to memory and naive T cells

Abstract

The cellular basis of immunological memory, particularly with respect to T cells is not understood. In humans, monoclonal antibodies to CD45 have been used to identify memory (CD45R0) and naive (CD45RA) T cells. However, this identification has been called into question by various studies which suggest that high molecular weight CD45 isoforms may be re-expressed by previously activated cells. In the present study, using cultures which supported responses of naive T cells, we examined the responses of purified CD45R0brightRA- or CD45R0(-)-RAbright T cell subsets. The former subset was found to respond preferentially to recall antigens with minimal responses apparent to neo-(or non-recall)-antigens. The inverse pattern was found for CD45R0-RAbright T cells, which converted to CD45R0brightRA- after stimulation with a neo-antigen. Moreover, the two populations of T cells exhibited distinct response kinetics with a faster response evident from the CD45R0brightRA- T cells compared to the CD45R0-RAbright subset. The poor responses of CD45R0-RAbright T cells to recall antigens compared to neo-antigens suggests that this putative naive population is specifically depleted of reactive T cells following an encounter with antigen. We propose that T cell priming results in the stimulation of many CD45R0-RAbright T cells with various T cell receptor specificities from which memory T cells are selected for survival. If re-expression of higher molecular weight isoforms does occur in humans in vivo, our results suggest that R0 expression would be retained (CD45R0+RA+). Alternatively, if primed CD45R0-RAbright T cells exist, they are not prevalent in peripheral blood and thus may be sequestered within lymphoid tissues. Our data support the view that in human peripheral blood, CD45R0bright and CD45RAbright expression identify memory and naive CD4+ T cells, respectively.

Effector CD8+CD45RO−CD27−T cells have signalling defects in patients with squamous cell carcinoma of the head and neck

“…It was viewed by us as a potentially important manifestation of host antitumour defence. Furthermore, ex vivo stimulation of patients' PBMC with PMA/ ionomycin showed that the expanded CD8 + CD45RO À CD27 À subset contained precursors of IFN-g-producing cells, confirming the effector cell status of this population (Hamann et al, 1997;Young et al, 1997). However, we discovered that practically all of the T cells in the effector subset had low or no z expression.…”

“…Thus, we were especially interested in the fate of CD8 + CD45RO À CD27 À in patients with cancer. By multicolour flow cytometry, it was possible to differentiate between the naïve, memory and effector subsets of CD8 + T lymphocytes, using antibodies to well-recognised surface markers CD45RA and CD45RO in combination with CD27 or CD62L (Hamann et al, 1997;Young et al, 1997). Strikingly, we observed that the population of CD8 + CD45RA + CD27 À T cells was greatly expanded in the circulation of patients with SCC of the head and neck.…”

“…CD8 + T cells are functionally heterogeneous, and several subsets of CD8 + T cells are known to contribute to antitumour immune responses. In addition to an effector T cell subset, both naïve and memory CD8 + T cells exist within the peripheral CD8 + T-cell pool (Hamann et al, 1997;Young et al, 1997;Sallusto et al, 1999;Baares et al, 2000).…”

“…Human naïve and memory T cells can be identified by the reciprocal expression of the CD45RA or CD45RO isoforms (Young et al, 1997). More recent reports indicate that within the CD8 + CD45RA + (CD45RO À ) compartment of naïve cells, a subset of effector T cells, which lack the CD27 receptor as well as the lymph node homing receptors CD62L and CCR7, can be identified (Hamann et al, 1997;Sallusto et al, 1999).…”

CD45 isoform expression is associated with different susceptibilities of human naive and effector CD4+ T cells to respond to IL‐4

“…The expression of CD45 isoforms served as marker for naive versus effector T cells. Although it is well known that T cells expressing CD45R0 may re-express CD45RA [31], CD45RA + CD45R0 -cells still fulfill a number of criteria for the definition of naive T cells [14,32]: (i) they produce IL-2 but no other cytokines following short-term activation; (ii) they respond to neo-but not recall antigens; and (iii) they express low levels of adhesion and homing molecules. In addition, re-expression of CD45RA on CD45R0 + T cells has been shown not to be associated with disappearance of CD45R0, suggesting that CD45RA + CD45R0 -expression on T cells is still a valid marker for human naive T cells [33].…”