Joel M. Depper

We studied purified subpopulations of lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) in order to determine whether intrinsic defects in lymphocyte function, aside from those due to alterations in lymphocyte numbers, were present. Mitogen-stimulated DNA synthesis, production of gamma interferon, production of interleukin-2, and expression of interleukin-2 receptors, although variably decreased in unseparated cell populations, were normal in populations of purified T-cell subsets. In contrast, DNA synthesis in response to the soluble protein antigen tetanus toxoid was decreased in both unseparated and purified T-cell subpopulations. Cell-mixing experiments demonstrated that the hyporesponsiveness of the unfractionated lymphocytes from patients with AIDS was not due to active suppression. We conclude that the lymphocytes of patients with AIDS, although capable of undergoing a normal degree of blast transformation and lymphokine production after mitogenic stimulation, have an intrinsic defect in their ability to recognize and respond to soluble antigen.

The gene encoding the human interleukin-2 (IL-2) receptor consists of 8 exons spanning more than 25 kilobases on chromosome 10. Exons 2 and 4 were derived from a gene duplication event and unexpectedly also are homologous to the recognition domain of human complement factor B. Alternative messenger RNA (mRNA) splicing may delete exon 4 sequences, resulting in a mRNA that does not encode a functional IL-2 receptor. Leukemic T cells infected with HTLV-I and normal activated T cells express IL-2 receptors with identical deduced protein sequences. Receptor gene transcription is initiated at two principal sites in normal activated T cells. Adult T cell leukemia cells infected with HTLV-I show activity at both of these sites, but also at a third transcription initiation site.

Abstract An empiric observation of the rapid development of B lymphoblast cell lines after in vitro infection with Epstein‐Barr virus (EBV) in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA) led us to compare cellular regulation of EBV‐induced lymphoblast outgrowth in RA and normal lymphoid cell populations. We found that RA PBM developed proliferating B lymphoblast colonies in a median time of 10 days after exposure to an EBV containing culture supernatant, while normal PBM took 18 days to grow out under the same conditions. The more rapid outgrowth of RA cells was not due to therapy with antiinflammatory or antirheumatic drugs. The time to outgrowth of the normal cells decreased to 11 days after T cell depletion. T cell depletion of the RA cells had less effect on the time to outgrowth but it was shortened to 8 days. B lymphoblast cell lines were established from “purified” T cell populations from 18 of 20 RA patients, while populations of T cells from normal donors with the same percentage of T and B cells did not produce lymphoblast cell lines when infected with EBV. In addition, we found that the non‐ T lymphoid cells from 7 of 20 RA patients established permanent B lymphoblast cell lines spontaneously without EBV infection. Spontaneous outgrowth of lymphoid cells from normal donors occurred only once in 48 experiments. These results indicate abnormalities in cell‐mediated regulation of EBV‐induced cell proliferation in lymphoid cells from patients with RA.