Immune memory in CD4(+) CD45RA(+) T cells

This study addresses the question of whether human peripheral CD4(+) CD45RA(+) T cells possess antigen-specific immune memory. CD4(+) CD45RA(+) T cells were isolated by a combination of positive and negative selection. Putative CD4(+) CD45RA(+) cells expressed CD45RA (98.9%) and contained <0.1% CD4(+) CD45RO(+) and <0.5% CD4(+) CD45RA(+) CD45RO(+) cells. Putative CD45RO(+) cells expressed CD45RO (90%) and contained 9% CD45RA(+) CD45RO(+) and <0.1% CD4(+) CD45RA(+) cells. The responder frequency of Dermatophagoides pteronyssinus-stimulated CD4(+) CD45RA(+) and CD4(+) CD45RO(+) T cells was determined in two atopic donors and found to be 1:11314 and 1:8031 for CD4(+) CD45RA(+) and 1:1463 and 1:1408 for CD4(+) CD45RO(+) T cells. The responder frequencies of CD4(+) CD45RA(+) and CD4(+) CD45RO(+) T cells from two non-atopic, but exposed, donors were 1:78031 and 1:176903 for CD4(+) CD45RA(+) and 1:9136 and 1:13136 for CD4(+) CD45RO(+) T cells. T cells specific for D. pteronyssinus were cloned at limiting dilution following 10 days of bulk culture with D. pteronyssinus antigen. Sixty-eight clones were obtained from CD4(+) CD45RO(+) and 24 from CD4(+) CD45RA(+) T cells. All clones were CD3(+) CD4(+) CD45RO(+) and proliferated in response to D. pteronyssinus antigens. Of 40 clones tested, none responded to Tubercule bacillus purified protein derivative (PPD). No difference was seen in the pattern of interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) producing clones derived from CD4(+) CD45RA(+) and CD4(+) CD45RO(+) precursors, although freshly isolated and polyclonally activated CD4(+) CD45RA(+) T cells produced 20-30-fold lower levels of IL-4 and IFN-gamma than their CD4(+) CD45RO(+) counterparts. Sixty per cent of the clones used the same pool of V beta genes. These data support the hypothesis that immune memory resides in CD4(+) CD45RA(+) as well as CD4(+) CD45RO(+) T cells during the chronic immune response to inhaled antigen.