Modulation of HTLV-II-Associated Spontaneous Lymphocyte Proliferation by β2 Integrin CD11a/CD18 Involves Interaction with Its Cognate Ligand, CD54

In vitro culture of lymphocytes from persons infected by human T-lymphocyte virus type II (HTLV-II) results in spontaneous proliferation in the absence of any exogenous stimuli. The present investigation examined the role of integrin molecules in spontaneous lymphocyte proliferation (SLP) in persons infected with HTLV-II (n = 18) and normal controls (n = 16). Phenotypic analysis of SLP cells on Day 8 demonstrated no change in the surface expression of CD29 (β1), CD49b,d,e, and f (α-chains) compared with cells from normal controls; however, there was an increase of CD29 expression on SLP cells on Day 8 (77.2 ± 5.1%) compared with Day 0 (53.2 ± 3.1%; P < 0.01). Furthermore, addition of extracellular matrix proteins, fibronectin, laminin, or collagen (β1 integrin ligands) did not alter either the proliferative responses or the adhesion clusters in either groups. Analysis of β2 integrins on SLP cells showed not only an increased cell surface density of both CD18 and CD11a but also differential expansion of CD8+ T-cells coexpressing CD18 (54.0 ± 10.3%), CD11a (53.7 ± 8.1%), and S6F1, an epitope of CD11a, (65.3 ± 7.8%) on Day 8 compared with Day 0 (20.0 ± 2.5%, 19.3 ± 1.9%, and 38.0 ± 7.0%, respectively). Monoclonal antibodies to CD18 and CD11a inhibited SLP by 55 ± 6.3% in HTLV-II-infected persons in a dose-dependent manner. The inhibition of SLP by anti-β2 antibodies was not due to negative signaling, since these antibodies did not inhibit anti-CD3-stimulated proliferation of normal lymphocytes. Moreover, monoclonal antibodies to CD54, the ligand for CD11a, inhibited the SLP in the majority of HTLV-II-infected persons studied. Taken together, these data suggest that SLP by PBL from HTLV-II-infected individuals is mediated through increased expression of β2 integrins that can modulate cognate receptor/ligand interactions on the cell surface of autologous proliferating cells.