Immunophenotypic characterization of peripheral T lymphocytes inMycobacterium tuberculosisinfection and disease

Abstract

SUMMARYThe cellular immune response probably plays a pivotal role in determining the clinical outcome after exposure to Mycobacterium tuberculosis. We used multi-parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets during infection and disease caused by M. tuberculosis. Samples were obtained from 71 volunteers to identify the T CD4 + and CD8 + lymphocyte numbers, and the activation plus memory/naïve phenotypes, as defined by CD38, HLA-DR, CD45RA and CD27 markers. Subjects were divided into 18 healthy volunteers without detectable reaction to purified protein derivative (PPD -), 18 health care workers with a recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC) and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison analyses, the T CD4 + lymphocyte number of the TBC group was lower than the PPD -group (P < 0·05). This difference was apparently lost after treatment. The higher and the lower number of naïve T CD4 + cells was observed in the PPD -and TBC group, respectively. CD8 + T lymphocytes were also statistically different among the four groups (P = 0·0002), lower in the TBC group (P < 0·05). CD8 + T lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression. The percentage distribution of these markers was statistically different between the four groups (P = 0·0055). TBC patients had a higher percentage of CD38 + cells and mean fluorescence index, suggesting an overall increase of cell activation. These results suggest that peripheral T lymphocytes reflect cellular activation during TBC, along with possible redistribution of naïve, memory/effector and late differentiated memory/effector phenotypes in the peripheral blood after infection and disease caused by M. tuberculosis.

CD4+ cell counts in patients with different clinical manifestations of tuberculosis

“…The results showed that patients with pulmonary tuberculosis had lower CD4 counts than control group. CD4 lymphocytopenia had been previously shown in both smear positive [3,[9][10][11] and smear negative [9] pulmonary tuberculosis. Another study revealed increased CD4+ T lymphocytes in BAL fluid of patients with less advanced non-cavitary pulmonary tuberculosis and significant enhancement in percentage of CD8+ cells in severe cavitary forms [7].…”

“…Several hypotheses have been postulated for diminished number of CD4+ cells in tuberculosis. Lymphocytes homing in affected tissue rather than circulation, increased apoptosis level [3] or impaired thymus function [16] are some examples.…”

“…The results of other researches were somehow conflicting. Some studies showed normal CD8 values in patients [11,13], some increased [9] and some decreased values [3]. Recent studies suggest that CD8 T-cells have distinctive role in immunity against Mycobacterium tuberculosis, for example they preferentially use granule exocytosis pathway and recognize heavily infected cells [5], ingest macrophages that have engulfed mycobacteria [7], secrete cytokines and lyse infected cells [6].…”

“…It has been shown that CD4+ T-lymphocytes are most important in the protective response against Mycobacterium tuberculosis. In murine studies, T-cell deficiency was associated with increased susceptibility to disease [2][3][4]. Increased frequency and severity of tuberculosis in HIV positive patients is another good evidence of importance of CD4+ T-cells in control of this infection.…”

Clinical forms and outcome of tuberculosis in HIV-infected patients in a tertiary hospital in São Paulo - Brazil

“…This trend was not sustained at the following assessments, as apparently random increases and decreases were observed. It is known that TCD 8 + cell counts are reduced in patients with TB without HIV infection and are even lower in co-infected patients [52]. It was observed in a trial conducted in Brazil with 61 patients, 20 with TB, 10 infected with HIV, 14 co-infected and 17 healthy individuals, that isolated TB was the disease associated with the lowest counts of TCD 8 + cells [53].…”