Reactivity toward soluble recall antigens (Candida albicans, cytomegalovirus, herpes simplex, streptokinase-streptodornase, and influenza) was determined in cultures of peripheral blood mononuclear cells from 41 rheumatoid arthritis patients (with clinically active as well as inactive disease) and from 28 controls. In the group with clinically active rheumatoid arthritis we found an increased incidence of "anergy," defined as nonreactivity to three or more antigens. In an attempt to explain this decreased antigen reactivity, the latter was correlated with peripheral blood lymphocyte subsets, as defined by two-color immunofluorescence with a panel of eight monoclonal antibodies. We found a significantly lower number of memory T4 cells (CD4+CD45RA-) and a significantly higher number of the CD3-CD57+ (nonspecific suppressor) cells and of CD3-CD56+/CD16+ (natural killer) cells in anergic RA patients. In the total group of rheumatoid arthritis patients, the antigen reactivity correlated positively with the percentage of memory T4 cells. Antigen reactivity was negatively correlated with the percentage of CD3-CD57+ cells and of the CD3- natural killer cells in peripheral blood. Our data suggest that a decrease in memory T4 cells and an increase in nonspecific suppressor cells may contribute to the impaired cellular immune function in peripheral blood of rheumatoid arthritis patients.

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Common variable immunodeficiency (CVI) with hypogammaglobulinemia is often complicated by nodular lymphoid hyperplasia of the intestine. In this study the lymphoid constituents of intestinal nodular hyperplasia of five CVI patients were characterized with monoclonal antibodies. Few CD4(+) but abundant CD8(+) T lymphocytes were found around the follicles. The follicles were populated mainly by B cells expressing surface IgM. A few cells in the lamina propria expressed Leu7. No intracytoplasmic immunoglobulin-containing plasma cells were seen. Peyer's patches in gut biopsies from controls were also composed of follicles with B lymphocytes. A ring of T lymphocytes surrounded the follicles. CD4(+) helper cells largely outnumbered CD8(+) cells in this ring. Moreover, plasma cells were present in the lamina propria and the mixed cell zone covering the follicles. In peripheral blood of the patients, B cells were present in normal proportions but they could not be induced to produce IgG in vitro by T cell-dependent (pokeweed mitogen) or T cell-independent (Staphylococcus aureus Cowan I) mitogens. In two of the patients, IgM production could be induced in vitro. Peripheral blood T cells were predominantly CD8(+) in three of the five patients, and in these same patients an increase in suppressor-cell activity of peripheral blood T cells on immunoglobulin production was observed. The data demonstrate a block in B-cell differentiation in the gut and in peripheral blood. Whether the local increase in CD8(+) cells in the nodular lymphoid hyperplasia is a primary event or is secondary to chronic immune stimulation and whether it contributes to local inhibition of B-cell differentiation remain to be investigated.

We evaluated the effects of a nonsteroidal antiinflammatory drug, naproxen, on phytohemagglutinin (PHA)–induced lymphocyte proliferation. When added in vitro to cultures of peripheral blood mononuclear cells, naproxen enhanced the proliferative response toward PHA of lymphocytes from rheumatoid arthritis (RA) patients but not from healthy volunteers, and it reduced prostaglandin E2 (PGE2) synthesis in the cultures. Oral treatment for 7 days with naproxen also resulted in a significant enhancement of the in vitro PHA‐induced proliferation of lymphocytes from RA patients and from age‐matched control patients with noninflammatory rheumatic diseases, but not from young healthy controls. This enhancement of PHA‐induced lymphocyte proliferation after oral intake of naproxen was not accompanied by diminished in vitro PGE2 production in the cultures. It did occur when PGE2‐producing monocytes were removed and when in vitro PGE2 synthesis was blocked with indomethacin. We conclude that oral treatment with naproxen has an immunomodulatory effect and improves in vitro PHA‐induced proliferation of lymphocytes from rheumatic disease patients. This effect is not due to reduced PGE2 synthesis in the in vitro cultures, but reflects a more fundamental in vivo change in immunoregulation.

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