Differential role of CD28 and CD27 in human CD4 T cells primary and secondary responses to bacterial antigens.

Abstract Although CD28 is considered the main T cell costimulatory molecule, CD27 has also costimulatory activity; nevertheless, it is not well established whether they play overlapping or complementary roles during CD4 T cell activation. Both molecules are co-expressed on a large percentage of CD4 T cells, mainly in naive and central memory T cells; but their ligands, CD80/CD86 and CD70 respectively, are differentially expressed on antigen presenting cells. To further differentiate the costimulatory role of CD28 and CD27 in the human CD4 T cell responses, circulating T cells from healthy donors were stimulated with Mycobacterium tuberculosis Purified Protein Derivative (PPD) under conditions of selective blockade of CD80 and CD86 or CD70 binding. The costimulatory activities of CD28 and CD27 in CD4 T cells memory responses were compared by stimulating PBMC, from tuberculin positive (TST+) donors, with PPD in the presence of either anti-CD80 plus anti-CD86 or anti-CD70 and then measuring CD4 T cells proliferation, IFN-gamma production and CD30 expression by flow cytometry. Treatment with anti-CD80 plus anti-86 inhibited all CD4+ T cell responses, but anti-CD70 had no effect. To study their role in the CD4+ T cell primary responses, myeloid dendritic cells, from TST negative donors, were pulsed with PPD and cocultured with autologous T cells under the blockade conditions described above. Anti-CD80 plus anti-CD86 as well as anti-CD70 inhibited CD4+ T cell proliferation and CD30 expression. These results support that CD28-CD80/CD86 signals are needed for both primary and memory CD4 T cell responses, whereas CD27-CD70 signals are required mainly for the primary anti-PPD responses. (Supported by Colciencias, Colombia, contract 0275-2014).