CD4+ T Lymphocytopenia and Depressed Lymphoproliferative Response in Latent Tuberculosis

             Approximately 1.7 billion people, or a third of the worldâs population, are infected with Mycobacterium tuberculosis (MTB), and tuberculosis (TB) is the leading cause of death from a single pathogen worldwide.  More than 95% of the 8 million annual cases of TB occur in developing countries, and the largest number of cases (estimated at 5 million) is found in Asia.  In the United States, TB cases are reported principally from urban areas among ethnic minorities and foreign-born immigrants.  Cell-mediated immunologic abnormalities in patients with active TB include CD4+ T lymphocytopenia and depressed lymphoproliferative response to MTB antigens.  To determine if similar aberrations occur in latent TB, flow cytometric analysis of T-cell subsets was performed in healthy adults who exhibited skin test reactivity to purified protein derivative (PPD).  Significant reductions in CD4+ T cells were found among 10 PPD skin test-reactive individuals, when compared to 12 PPD-nonreactive study subjects (P=0.0012).  Concurrently, g/d T cells were increased (P=0.0006) and the CD4/CD8 ratio (P=0.029) was decreased in the former group.  No gender- or ethnic-specific differences were found.  The CD4+ T-cell lymphoproliferative response to in vitro stimulation with phytohemagglutinin was significantly depressed in the PPD-skin test-reactive group (P=0.027).  Abnormalities in T-lymphocyte subpopulations were more pronounced among individuals immunized during infancy with bacille Calmette-GuŽrin.  Our data indicate that the immunologic perturbations observed in active TB may already exist during latency.  Further studies are underway to assess T-cell subsets in various ethnic groups (including Chinese, Japanese and Filipino) based on their BCG immunization history and PPD skin test status.

Yin, C.Q., Nerurkar, V.R., Kimura, L.H., Dashwood, W-M., Johnson, A.C., III, and Yanagihara, R.:  CD4 T lymphocytopenia and depressed response in latent tuberculosis.  Hawaii Medical Journal (in preparation)

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