Although directly microbicidal, pentavalent antimony has failed as treatment for visceral leishmaniasis in patients who also have AIDS or are receiving immunosuppressive therapy. To define the role of T cells in the successful host response to chemotherapy, we examined the efficacy of pentavalent antimony (sodium stibogluconate, Pentostam) in normal and T cell-deficient BALB/c mice infected with Leishmania donovani. In euthymic (nu/+) mice, single injections of 250 and 500 mg/kg of Pentostam induced the killing of 67% and 89% of intracellular liver amastigotes, respectively. In contrast, in athymic nude (nu/nu) mice, up to three injections of 500 mg/kg achieved no L. donovani killing and did not retard visceral parasite replication. Once nude mice were reconstituted with nu/+ spleen cells, however, Pentostam exerted strong leishmanicidal activity, an effect that appeared to be transferred by either L3T4+ or Lyt-2+ cells. Responsiveness to chemotherapy could also be induced by providing nude mice with either interferon-'y or interleukin 2 alone. The absence of this T cell-and probably lymphokine-dependent mechanism is a likely explanation for treatment failures in immunocompromised patients infected with L. donovani and perhaps other systemic intracellular pathogens as well.
In contrast to euthymic (nu/+) BALB/c mice, athymic nude (nu/nu) BALB/c mice fail to control the visceral intracellular replication of Leishmania donovani, do not generate the macrophage-activating lymphokine IFN-gamma, and show little or no granulomatous tissue response. To characterize the T cell requirement for successful defense against L. donovani, nude mice were first reconstituted with unfractionated nu/+ immune spleen cells, which readily conferred the capacity to control and eliminate visceral (hepatic) L. donovani. In reconstituted mice, acquired resistance was paralleled by the ability of spleen cells to generate high levels of leishmanial Ag-stimulated IFN-gamma and the development of well formed liver granulomas. In contrast, nude mice reconstituted with either L3T4+- or Lyt-2+-enriched immune spleen cells alone failed to control visceral parasite replication and did not develop effective granulomas despite the finding that transfer of L3T4+ cells largely and Lyt-2+ cells partially restored the capacity to secrete IFN-gamma. To determine whether both T cell subsets were also required in a normal host, nu/+ BALB/c mice were treated with cell-depleting anti-L3T4 and anti-Lyt-2 mAb. Depletion of either T cell subset inhibited the acquisition of resistance to L. donovani and impaired the tissue granulomatous response. Thus, successful T cell-dependent host defense towards intracellular L. donovani and the tissue expression (granulomas) of this mechanism appear to require both L3T4+ and Lyt-2+ cells. A primary role for the L3T4+ cell may be IFN-gamma production; the role of the Lyt-2+ cell and the precise interaction of the two T cell subsets remain to be identified.
Multiple sclerosis (MS) and necrotizing periodontitis (NP) are two diseases whose aetiology and pathophysiology do not seem to have a common link; however, the treatment of MS with monoclonal antibodies and the decrease in humoral immunity that this entails can be a trigger or an aggravation in patients who present NP. We present a clinical case of NP in which its clinical manifestations, treatment and evolution during therapy with ocrelizumab are reflected. During the evolution of the case, a rapid progression of NP was evidenced. During her evolution, the patient suffered bilateral pneumonia due to COVID requiring treatment with corticosteroids and antibiotics, which led to clinical relief of her NP. Given this important clinical finding, we consider of great interest the regulated dental monitoring of those patients with MS before, during and after the administration of monoclonal antibodies to prevent periodontal deterioration.
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