Primary and secondary human in vitro T-cell responses to soluble antigens are mediated by subsets bearing different CD45 isoforms

A culture system has been developed which consistently supports in vitro proliferative responses to conventional soluble antigens by human CD4⁺ T cells from non-immunized donors. T cells exposed to an antigen in primary cultures could be restimulated in vitro in an antigen-specific manner to give secondary responses with greater magnitudes and a more rapid onset than the initial reaction. To characterize further the responding T-cell population in primary compared with secondary reactions, T cells were depleted of CD45RA⁺ or CD45RO⁺ cells and stimulated with recall and non-recall antigens. It was found that the soluble non-recall antigen keyhole limpet haemocyanine did not stimulate CD45RO⁺ T cells, yet induced strong proliferative responses from CD45RA⁺ T cells. Conversely, it was confirmed that human CD45RO⁺ T cells respond to the recall antigen-purified protein derivative from Mycobacterium tuberculosis. Cell mixing experiments indicated that CD45RO⁺ T cells are unlikely to have any suppressive effect on the reactivity of CD45RA⁺ cells to non-recall antigens. These data provide new support for the hypothesis that CD45RA⁺ represents the naive and CD45RO⁺ the memory phenotype of human CD4⁺ T cells.