Nobuo Morikawa

Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with Cryptococcus neoformans

A quantitative and qualitative change in inflammatory cells in the lungs of mice after intratracheal inoculation of heat‐killed Cryptococcus neoformans was examined by direct analysis of the pulmonary intraparenchymal leucocytes. Macrophages and T and B lymphocytes increased, peaked at day 7, and then gradually decreased to the basal level, Macrophages were activated 7 days after the inoculation, as indicated by the enhanced expression of MHC class II, intercellular adhesion molecule‐1 (ICAM‐I)and Fc receptor (FcR), which have been known as their activation markers. T cells were also activated, as indicated by the induction of IL‐2 receptor (IL‐2R) and the enhanced expression of leucocyte function‐associated molecule‐1 (LFA‐1) and ICAM‐1, a pair of adhesion molecules which have also been regarded as T cell activation markers. CD4+ T cells preferentially accumulated in lungs, and proliferated in vitro by stimulation with heat‐killed whole yeast cells, suggesting that at least some of the infiltrated T cells expand locally in response to the organisms. These results demonstrate that the activation of macrophages and T cells reactive to C. neoformans is induced in lungs after intratracheal inoculation of heat‐killed organisms, and suggest that these cells interact to eliminate organisms more efficiently from the host.

Increase in T-cells bearing CD25 in bronchoalveolar lavage fluid from HAM/TSP patients and HTLV-I carriers.

To determine the immunologic characteristics of T‐cells in local pulmonary lesions of human T‐cell lymphotropic virus type I (HTLV‐I) carriers, we investigated lymphocyte surface markers in peripheral blood and bronchoalveolar lavage fluid (BALF) of 38 HTLV‐I carriers, 8 HTLV‐I associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 44 HTLV‐I seronegative patients with pulmonary diseases and 7 healthy volunteers using two‐color flow cytometric analysis. In peripheral blood, activated T‐cells, CD4+HLA‐DR +, CD8 + HLA‐DR + and CD3 + CD25 +, and CD4+CD29+ cells increased significantly in carriers and HAM/TSP patients compared with healthy volunteers and seronegative patients. In BALF, T‐cells, especially CD25+ cells, increased significantly in carriers and HAM/TSP patients, compared with healthy volunteers and seronegative patients. These findings indicated that T‐cells in the lungs, as well as in peripheral blood, are activated in carriers and HAM/TSP patients. Interestingly, there was dissociation between expression of CD3 + CD25+ cells in BALF and peripheral blood from these patients. These results suggest that T‐cells activated probably by HTLV‐I accumulate in the lungs in some carriers and HAM/TSP patients, and HTLV‐I may be involved in the immunologic dysfunction in the lungs of these patients. However, we did not find any correlation between the degree of clinical features and the elevation of CD3 + CD25+ cells in BALF, or its characteristic features on chest roentgenograms.