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Progressive changes have been reported in lymph nodes in HIV infection, but few accounts describe altered splenic histology at different stages of the disease. Investigation of splenic changes accompanying the progressive CD4+ T-cell depletion that occurs in HIV infection could shed light on normal immunological interactions in this organ. Therefore, we assessed the amount and distribution of lymphoid tissue in spleens from adults with documented early or advanced HIV disease.Immunohistochemistry was used to study splenic tissue collected in an extensive autopsy survey of HIV+ adults in West Africa. Compared with post-mortem spleens from HIV– West African adults and control UK spleens, those from HIV-infected patients showed severe atrophy of white pulp B- and T-cell compartments. In early and advanced HIV disease, marginal zone atrophy was significant. Peri-arteriolar lymphoid sheaths contained increased numbers of CD8+/CD45RO+ T-cells in advanced HIV disease. In red pulp, early and advanced cases showed a lymphocytosis of CD8+/CD45RO– T-lymphocytes.Atrophic changes were more extreme in advanced than early HIV infection. Reduced marginal zone function possibly explains the known predisposition of HIV+ patients to infection by encapsulated bacteria. Possible immunological consequences of these CD8+/CD45RO+ (peri-arteriolar lymphoid sheaths) and CD8+/CD45RO– (red pulp) responses deserve further study. Comparison of West African and UK control spleens indicated that there were no major ethnic differences in spleen structure to prevent extrapolation of our results to European adults.