Phenotypic analysis of complement receptor 2⁺ T lymphocytes: Reduced expression on CD4⁺ cells in HIV-infected persons

While expression of complement receptor 2 (CR2) (CD21) on some CD4⁺ cell lines renders them more susceptible to infection by complement-treated human immunodeficiency virus (HIV), co-expression of CR2 and CD4 on peripheral blood lymphocytes has not, until recently, been observed. Several recent studies, however, have found that human T lymphocytes express low levels of CR2. Additionally, complement treatment of HIV before addition to these cells has been reported to increase virus expression in peripheral blood lymphocyte cultures. These findings suggest that complement-mediated enhancement of infection of human T cells could occur in vivo and have prompted us to examine both the phenotypic properties of CD4⁺ CR2⁺ T cells in healthy persons and the expression of CR2 on CD4⁺ lymphocytes during HIV infection. As was previously reported, we observed CR2 on a proportion (10-50%) of both CD8⁺ and CD4⁺ T cells. Approximately half of CD4⁺CR2⁺ cells expressed the memory cell markers CD45RO and CD29, 80% expressed the naive marker CD45RA, while 22% expressed CD25. These values were not substantially different from total CD4⁺ cells. Stimulation of lymphocytes with phytohaemagglutinin (PHA), OKT3 or calcium ionophore but not with phorbol myristate acetate (PMA) or interleukin-2 (IL-2) decreased expression of CR2 on CD4 cells by half over a 3-day culture period. The per cent of CD4⁺ cells expressing CR2 was significantly decreased in patients with asymptomatic and symptomatic HIV infection compared to uninfected control donors (P = 0.0001). In contrast, the decrease in CR2 expression was not observed with CD8⁺ lymphocytes from HIV-infected persons. These results confirm that CR2 is expressed on human T lymphocytes and suggest that a subset of CD4⁺ lymphocytes is selectively affected in HIV-infected individuals.