Engagement of CD45 during in vitro priming enhances antigen-specific Th cell frequencies

CD45 is a transmembrane protein tyrosine phosphatase expressedby all lymphoid cells including T cells. Substantial experimentaldata has shown that CD45 maintains a permissive state for TCRsignaling. The highly glycosylated extracellular domain of CD45may be the site of Interaction with regulatory lectin-like counter-receptorson antigen-presenting cells. The mAb NDA5, recognizing a uniquebut broadly distributed epitope of CD45, was used to study thepossible immunoregulatory role of CD45 during antl-CD3 and antigen-specificCD4⁺ T cell activation. In vitro priming of peripheral bloodmononuclear cells with peptlde antigens in the presence of mAbNDA5 results in a higher frequency of antigen-specific T cells.The responses of both naive and memory T cells to peptide antigenswere sensitive to mAb NDA5-enhanced priming. Anti-CD3 activationof normal resting T cells, in the presence of mAb NDA5, resultedIn enhancement of tyrosine phosphorylation of specific intracellularproteins associated with TCR signal transduction. In cultureswithout antigen, mAb NDA5 down-regulated the cell surface expressionof both CD3 and CD4, yet did not stimulate proliferation ofresting T cells. Together these results suggest that engagementof CD45 during in vitro priming has a significant effect onthe development of antigen-specific T cell populations.