CD4+CD45RA+T cells from adults respond to recall antigens after CD28 ligation |
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Authors: | Pilling Darrell; Akbar Arne N; Bacon Paul A; Salmon Mike |
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Institution: | Department of Rheumatology, The university of Birmingham Birmingham B15 2TT, UK
1 Department of Clinical Immunology, Royal Free Hospital, Pond Street, London NW3 2PF,UK |
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Abstract: | The leukocyte common antigen isoforms CD45RA and CD45RO havelong been used to discriminate human naive and memory T cellsrespectively. This model was largely based on the observationthat CD45RO+ T cells respond preferentially to and show a higherfrequency of precursors specific for recall antigens. However,CD45RA+ T cells have more stringent requirements for stimulationand standard in vitro assays may favour CD45RO+ cells in thisrespect. We tested the hypothesis that CD45RAf T cells respondpoorly to in vitro stimulation with recall antigens becauseof inadequate stimulation rather than a lack of precursors.Limiting dilution analyses (LDA) for tetanus toxoid (lT)-specificT cells were performed in the presence or absence of exogenousantLCD28 antibody. Addition of antLCD28 yielded no proliferationin the absence of specific antigen. The precursor frequencyfor lT in the CD4+ CD45RO+ population was –1:4000, whilethe frequency of CD4+ CD45RA+ T cells specific for lT was 4-to >>20-fold lower. Addition of anti-CD28 antibody didnot significantly alter the apparent precursor frequency forCD45RA+ cells but yielded an enhancement of the value for CD45RA+cells by 3- to >>5-fold. No enhancement of antigen-specificproliferation by antLCD28 was observed with CD45RA+ T cellsderived from cord blood, although phytohemagglutinin responsesof these cells were amplified by CD28 antibody. These resultsindicate that conventional LDA underestimate the true precursorfrequency of antigen-specific cells within the adult CD45RA+population and support the possibility that a small number ofcells revert from a primed (CD45RO+) to an unprimed (CD45RA+)state. The majority of memory T cells, however, appear to residein the CD45RO+ population |
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Keywords: | CD28 CD45 co-stimulation immunological memory T cell activation |
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