HUMAN NAIVE AND MEMORY T-HELPER CELLS DISPLAY DISTINCT ADHESION PROPERTIES TO ICAM-1, LFA-3 AND B7 MOLECULES

In this paper the contribution of different accessory molecules to the adhesion of resting, naive and memory CD4+ T cells was examined utili zing a panel of CHO cell transfectants as model antigen-presenting cel ls (APCs). CD4+ T lymphocytes demonstrated strong adhesion to HLA-DR4 transfected CHO cells co-expressing B7, ICAM-1 or LFA-3 molecules, sug gesting that all three adhesion pathways is utilized by resting CD4+ c ells. Monoclonal antibodies (MoAbs) against the corresponding receptor s on T cells, e.g. anti-CD28, anti-LFA-1beta and anti-CD2, inhibited c ompletely T-cell adhesion to natural ligands expressed on transfected CHO cells. Pretreatment of CD4+ T cells with NKI-L16 MoAb, which inter act with an activation epitope on LFA-1alpha chain, enhanced adhesion to ICAM-1 but not B7 or LFA-3-expressing CHO cells. Analysis of T help er-cell subsets revealed that memory T cells bound several fold strong er to ICAM-1 expressing transfectants compared to the CD4+ 45RA+ naive T cells, whereas adhesion to B7, LFA-3- and B7/LFA-3-expressing CHO c ells was similar in both T-cell subsets. The kinetics of adhesion of n aive and memory CD4 + T cells to ICAM-1 was rapid and similar in both subsets. The NKI-L16 MoAb multiplied several times ICAM-1-dependent ad hesion in naive compared to memory cells, which enabled the naive cell s to reach a similar adhesion level as memory cells. The results sugge st that resting naive CD4+ T cells utilize preferentially the CD2/LFA- 3 or CD28/B7 adhesion pathways upon adhesion to APCs, while memory CD4 + T cells utilize the CD2/LFA-3, CD28/B7 and LFA- 1/ICAM-1 adhesion pa thways. The NKI-L16 MoAb-induced upregulation of adhesion involves an increased affinity of LFA-I for its ligand and not a change in the num ber of LFA-I molecules. This is compatible with a view that naive cell s express a, large number of inactive LFA-1 molecules, whereas memory cells express preferentially activated LFA-1 molecules. The inherent l ow number of active LFA-1 molecules on naive CD4+ T cells may be impor tant in keeping these cells in a resting state.