Abstract

Introduction: Immune reconstitution syndrome is a potentially fatal sequelae of HAART therapy in 20% of patients with HIV and 3–5% with tuberculosis who begin treatment. The role of CD4+T cells in its pathogenesis is poorly understood.

Methods: This study was done under an IRB approved protocol to study MTb specific immunity. Groups based on HIV status and local or disseminated MTb were evaluated for CD4+ T cell counts, Purified Protein Derivative (PPD) induced proliferation and cytokine induction using intracellular cytokine staining for IFN γ, IL2, TNFα and CFSE dilution at predefined times before and after starting therapy.

Results: In preliminary results, the first 3 HIV negative patients with MTb exhibited striking increase in MTb specific immunity in the first week of therapy. Percentage of IFN γ producing CD4+T cells increased from 1.96 and 0.48 to 4.46 and 1.34, and of TNF α producing cells increased from 0.85 and 0.45 to 3.96 and 1.06 in 2 patients. Proliferative responses also showed marked increases. Percent dividing cells increased from 4.3, 4.4 and 16.3 at baseline to 36.9, 11.9 and 39.6 at 1 week and 54.8 and 72.3 at 4 weeks of therapy. Total number of CD4+ T cells also increased.

Conclusions: Tuberculosis like HIV causes quantitative and qualitative changes in CD4+T cells . These are rapidly reversed when therapy is begun .This data provides insight into the pathogenesis of the immune reconstitution syndrome.

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