CD4+ CD45RA+ T cells from adults respond to recall antigens after CD28 ligation.
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
The leukocyte common antigen isoforms CD45RA and CD45RO have long been used to discriminate human naive and memory T cells respectively. This model was largely based on the observation that CD45RO+ T cells respond preferentially to and show a higher frequency of precursors specific for recall antigens. However, CD45RA+ T cells have more stringent requirements for stimulation and standard in vitro assays may favour CD45RO+ cells in this respect. We tested the hypothesis that CD45RA+ T cells respond poorly to in vitro stimulation with recall antigens because of inadequate stimulation rather than a lack of precursors. Limiting dilution analyses (LDA) for tetanus toxoid (TT)-specific T cells were performed in the presence or absence of exogenous anti-CD28 antibody. Addition of anti-CD28 yielded no proliferation in the absence of specific antigen. The precursor frequency for TT in the CD4+ CD45RO+ population was approximately 1:4000, while the frequency of CD4+ CD45RA+ T cells specific for TT was 4- to > 20-fold lower. Addition of anti-CD28 antibody did not significantly alter the apparent precursor frequency for CD45RO+ cells but yielded an enhancement of the value for CD45RA+ cells by 3- to > 5-fold. No enhancement of antigen-specific proliferation by anti-CD28 was observed with CD45RA+ T cells derived from cord blood, although phytohemagglutinin responses of these cells were amplified by CD28 antibody. These results indicate that conventional LDA underestimate the true precursor frequency of antigen-specific cells within the adult CD45RA+ population and support the possibility that a small number of cells revert from a primed (CD45RO+) to an unprimed (CD45RA+) state. The majority of memory T cells, however, appear to reside in the CD45RO+ population.
