In the search for HLA-linked immune response genes that control susceptibility to tuberculosis, we performed HLA typing and measured antibody titers to well-defined Mycobacterium tuberculosis antigenic determinants in 101 patients with sputum smear-positive pulmonary tuberculosis and 64 healthy controls from Surabaya, Indonesia. HLA-DR2 and DQw1 were associated with sputum smear-positive pulmonary tuberculosis (attributable risk = 36% and 39%, respectively), while DQw3 was associated even more strongly with the control group (preventive fraction = 57%). Antibody titers to the TB71 and TB72 epitopes of the 38-kDa protein, present only on tubercle bacilli, were strongly associated with DR2 (Pcorr = .001 and .024, respectively). The association of both the disease and the antibody response to the 38-kDa antigen of M. tuberculosis with Class II HLA genes HLA-DR2 indicates that Ir-gene-mediated regulation of the immune response to this antigen may be of pathogenic significance for the development of sputum smear-positive tuberculosis.

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We studied the effects of herpes virus carrier status on peripheral blood T lymphocyte subsets in 334 healthy individuals. IgG-class antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella-zoster virus (VZV) were used as markers for the carrier status of those viruses. CMV carrier status was associated with significant increases in the numbers of some T cell subsets, whereas the carrier status of EBV, HSV, and VZV had no significant effects. The 159 CMV-seropositive individuals had higher numbers of HNK1+ T cells than did the 175 CMV-seronegative individuals [mean (SD), 292 (196)/microL v 164 (89)/microL, respectively], including the CD4+HNK1+ T cells [38 (48)/microL v 9 (13)/microL, respectively] and the CD8+HNK1+ T cells [166 (146)/microL v 73 (54)/microL, respectively]. Morphological and cytochemical studies showed that the expression of HNK1 by the CD4+ and CD8+ T cells was associated with the occurrence of azurophilic cytoplasmatic granules and a loss of nonspecific esterase activity. The numbers of CD4+HNK1+ and CD8+HNK1+ T cells increased proportionally to the levels of the IgG- class CMV antibody titers. We suggest that the increased numbers of CD4+HNK1+ and CD8+HNK1+ granular T cells in CMV carriers reflect the persistent interaction between CMV and the immune system of its hosts.

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An early decrease in the ratio between T4+ and T8+ T lymphocytes has been shown to correlate with the development of grade II-IV GVHD in allogeneic bone marrow transplant (BMT) recipients receiving methotrexate (MTX) as prophylaxis for acute graft-versus-host disease (GVHD). This study compares the onset of T-cell regeneration in patients receiving cyclosporin A (CyA) with those receiving MTX. Firstly, lymphoid recovery occurred at a significantly faster rate in the patients on CyA. Secondly, in those patients, the repopulation of T4+ and T8+ T cells started simultaneously, whereas in patients on MTX the repopulation of the T8+ subset lagged about a week behind that of the T4+ subset. Thirdly, the decrease in the T4/T8 ratios as a function of the lymphocyte counts occurred at a significantly slower rate in the patients on CyA than in those on MTX. Thus, the differences in the onset of T-cell regeneration in BMT recipients on CyA as compared with those on MTX abolished the correlation of the T4/T8 ratio changes with grades II-IV GVHD as described in patients receiving MTX.