Suppression of Cell-Mediated Immunity in Experimental African Trypanosomiasis

Abstract

Adult New Zealand white rabbits were experimentally infected with a parasitic African hemoflagellate, Trypanosoma congolense, and were subsequently tested for in vivo and in vitro aspects of cell-mediated immune function. Chronically infected rabbits were sensitized to mycobacterial protein and skin-tested with purified protein derivative; all infected animals demonstrated much milder skin-test responses to antigen than control groups. Similarly, peripheral blood lymphocyte responses in vitro to purified protein derivative and, as well, to phytohemagglutinin were markedly suppressed. Supernatant fluids of antigen-stimulated lymph node cell cultures from T. congolense-infected rabbits failed to demonstrate migration inhibitory factor activity but did possess normal levels-of blastogenic factor activity. An active infection was necessary for demonstration of suppressed immune responses, and components present in infected rabbit serum were apparently not responsible for the observed abnormalities. Suppression of T-lymphocyte subpopulations may well explain the occurrence of numerous immunological aberrations arising during human and animal infections with the African trypanosomes.

Regulation of innate and acquired immunity in African trypanosomiasis

“…Initial evidence for regulation of T‐cell proliferative and cytokine responses by African trypanosomes, as well as evidence for selective down‐regulation of T‐dependent B‐cell responses, led the way for dissection of immunosuppressive events in infection (62–64). Although disparate mechanisms were first proposed to explain suppression of T cells (65,66), it was ultimately clear that ‘suppressor macrophages’ and their products were generated by infection that exhibited a capacity to depress host T‐cell responses (4,6–8,11,12,67,68).…”

T‐lymphocyte requirement for the induction of mouse macrophage procoagulant activity by Trypanosoma brucei

“…1980), which suggests that trypanosomes may enhance antigen-specific lymphocyte functions. On the other hand, the proliferative response to lectins or unrelated antigens is rapidly abrogated (Jayawardena & Waksman 1977, Fierer & Askonas 1982, Mansfield & Wallace 1974, Pearson et al 1978. We found that by day 7 of infection, lymphocytes were producing enhanced amounts of lymphokine upon concanavalin A stimulation.…”

“…Cell-mediated immunity such as delayed type hypersensitivity and contact sensitivity reactions which involve immune T-lymphocytes appear to be depressed in chronic (Pearson et al 1978, Yamamoto et al 1985 but not in acute infections (Tizard & Soltys 1971, Freeman et al 1973, Urquhart et al 1973, Murray et al 1974b. To our knowledge, the only study to date on the production of lymphokines directed to macrophages comes from Mansfield & Wallace (1974) who showed that during T. congolense infection lymphocytes fail to secrete migration inhibitory factor.…”

Altered immune responsiveness associated with Encephalitozoon cuniculi infection in rabbits

“…The depression of the specific IgG response to an injected immunogen associated with a concurrent infection with E. cuniculi is paralleled by observations in other parasitic diseases (7,8,10). A number of mechanisms have been suggested to account for such observations in trypanosomiasis, including depression of By-cell function (16), depression of"helper" T-cell function (14), and macrophage dysfunction or anti- genic competition (20). The elevation ofthe specific IgM response toB.…”