Modulation of HTLV-II-associated spontaneous lymphocyte proliferation by beta 2 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 (beta 1), CD49b,d,e, and f (alpha-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 (beta 1 integrin ligands) did not alter either the proliferative responses or the adhesion clusters in either groups. Analysis of beta 2 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-beta 2 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 beta 2 integrins that can modulate cognate receptor/ligand interactions on the cell surface of autologous proliferating cells.