Reduction of Suppressor T Lymphocytes in the Tropical Splenomegaly Syndrome

Abstract

To study the pathogenesis of tropical splenomegaly syndrome, we compared immunologic findings in patients from Flores, Indonesia, with those obtained in local residents without splenomegaly and in controls. Villagers with tropical splenomegaly syndrome had markedly elevated levels of total IgM, higher titers of IgM antibodies to Plasmodium vivax, and reduced levels of circulating T lymphocytes. The latter were caused by a decrease in the total number of T cells with the suppressor/cytotoxic phenotype (T8+). Levels of B lymphocytes were similar in all groups. All immunologic abnormalities reverted toward normal in patients treated weekly for 9 to 26 months with chloroquine phosphate. These findings suggest that overproduction of immunoglobulins in patients with tropical splenomegaly syndrome is caused by an imbalance in the normal ratio of helper: suppressor T cells that regulate B-lymphocyte function, and that this imbalance is due to a decrease in suppressor T lymphocytes.

Antibody-mediated killing of suppressor T lymphocytes as a possible cause of macroglobulinemia in the tropical splenomegaly syndrome.

“…Wadee is the recipient of a fellowship from the South African Research Council. Address reprint requests to Dr. Piessens at the Harvard School of Public Health. Received for publication 21 September 1984 and in revised form 6 February 1985. munoregulatory thymus-dependent (T) lymphocytes in peripheral blood of patients with TSS, a finding that is consistent with this hypothesis (5). However, these studies failed to document that such phenotypic changes resulted in functional abnormalities that could account for the marked hyperproduction of IgM in patients with TSS.…”

“…This observation has prompted the hypothesis that the polyclonal gammopathy of TSS results from hyperproduction of immunoglobulins (mostly IgM) by B lymphocytes activated by malarial antigens or mitogens. This, in turn, is believed to reflect an imbalance in the number and/or activity of immunoregulatory T lymphocytes in patients with this syndrome (4,5). In a previous study, we found that Indonesian patients with TSS lacked circulatory lymphocytes of the T8' (suppressor/cytotoxic) phenotype (5 Although our studies indicate that actual destruction of suppressor cells may contribute to the immunoregulatory abnormalities associated with TSS, we cannot rule out the possibility that the anti-T cell antibodies that we describe could operate in vivo by noncytotoxic mechanisms, e.g., by altering lymphocyte traffic or homing patterns.…”

“…This, in turn, is believed to reflect an imbalance in the number and/or activity of immunoregulatory T lymphocytes in patients with this syndrome (4,5). In a previous study, we found that Indonesian patients with TSS lacked circulatory lymphocytes of the T8' (suppressor/cytotoxic) phenotype (5 Although our studies indicate that actual destruction of suppressor cells may contribute to the immunoregulatory abnormalities associated with TSS, we cannot rule out the possibility that the anti-T cell antibodies that we describe could operate in vivo by noncytotoxic mechanisms, e.g., by altering lymphocyte traffic or homing patterns. In this context, it is of interest that sera from patients with systemic lupus erythematosus contain both cytotoxic antibodies to suppressor T cells and antibodies that interfere with suppressor cell activity by a noncytolytic mechanism (13,14).…”

“…In a previous study, we enumerated circulating T and B lymphocytes in a large number of inhabitants of Robek, Flores, Indonesia, where TSS is common and in a group of residents of Jakarta, Java, Indonesia, where malaria is not transmitted (5). This information was used to select blood donors for the present study.…”

“…This information was used to select blood donors for the present study. All participants were adult volunteers assessed clinically and parasitologically as previously described (5 (8). In brief, cells from normal donors (see below) were labeled with Na5tCrO4 (New England Nuclear, Boston, MA) and washed extensively.…”