Lymphocyte apoptosis and immune response in patients with drug-resistant fibro-cavernous tuberculosis with different prevalence of destructive changes in the lungs

Disturbances of programmed cell death are at the heart of many immunopathological processes in tuberculosis. The relationship between activity of apoptosis and severity of immune response is of particular interest in the patients with fibrous-cavernous drug-resistant pulmonary tuberculosis at different extent of the process. The paper concerns features of apoptosis, proliferative activity of lymphocytes, cytokine’s production and subpopulation composition of peripheral blood lymphocytes in the patients with uni- and bilateral fibrous-cavernous drug-resistant pulmonary tuberculosis. It was shown that apoptotic rates in the examined patients is closely related to extent of pathological process. Extent of early and late apoptosis and, accordingly, the number of living cells reflected the progression degree of destructive process in the lungs affected by fibrous-cavernous tuberculosis. The possibility of predicting the extent of destructive changes in affected lungs based on expression of apoptosis markers is presumed. Index of activity for early apoptosis of T lymphocytes, exceeding normal values by 25% and higher were clinically significant. A clear relationship between the immune response and apoptosis level was revealed. Ambiguous changes of immunological parameters were shown with increasing apoptosis associated with the severity of destructive changes. Increased apoptotic cell death in all patients with fibrous-cavernous tuberculosis, regardless of extent of the process, was associated with inhibition of antigen-specific proliferative response, decrease in CD25+ lymphocytes, increased numbers of B cells, along with decreased production of IFNγ, IL-8, and increased IL-2 response to PPD. In cases of unilateral destruction, increased apoptotic rates were accompanied by a decrease in the CD95+ cell numbers, and a decrease in TNFα production. On the contrary, in patients with bilateral destruction it was characterized by a high content of CD95+ lymphocytes, increased production of TNFα and IL-10. An index of extremely unfavorable course of the process is a combination of high apoptosis levels and low antigen-specific response with low expression of CD25+ cells, increased number of CD19+ and CD95+ lymphocytes, decreased production of IFNγ, IL-8 and increased production of IL-2, TNFα, IL-10. The relationships found in the work indicate that the combined assessment of apoptosis indexes, together with immunological parameters, has a higher informative value when assessing the state of immunocompetent cells, the origin of the process and trends for its development. Detecting the features of programmed lymphocyte death, in conjunction with immune parameters, allows to evaluate the role of apoptosis in each single case and to predict the course of the process, with subsequent justification of immunotherapy administration

FEATURES OF SPECIFIC IMMUNE RESPONSE IN THE PATIENTS WITH FIBROUS/CAVERNOUS TUBERCULOSIS OF LUNGS

Abstract. The aim of the present study was to determine the different profiles of the immune responsiveness of the patients with fibro-cavernous pulmonary tuberculosis to PPD from M.tuberculosis in comparison with their response to standart mitogen and IFNγ. A pronounced specific Th1 response was found, evidenced by the enhanced proliferation and IL-2 and IFNγ production after contact of their peripheral blood mononuclear cells (PBMCs) with PPD. At the same time a high frequency of PPD-anergy was shown: сonsiderable proportion of TB patients was characterized by low proliferative response to PPD coupled with the low levels of IL-2 and IFNγ. Most of the patients revealed failure of monocyte/macrophage oxidative burst in response to PPD. Additionally a positive correlation was found between the levels of their PBMC’s oxidative burst and IL-4 production

IMMUNE INDEXES IN PATIENTS WITH PROGRESSIVE FIBROUS-CAVERNOUS TUBERCULOSIS DEPENDENT ON SEVERITY OF DESTRUCTIVE CHANGES IN THE LUNGS

Abstract. We have studied cellular immune state in patients with progressive fibrous cavernous tuberculosis (FCT) with varying severity of lung destructive changes. It was found that increasing number of specific cytotoxic lymphocytes, NK-, NKT-, CD95-cells and activated T-lymphocytes, accompanied by a significant decrease of T-helper cells, B cells, CD25-cells, is a sign of destruction, along with inhibition of antigen-specific cellular response and functional insufficiency of T-helper and cytotoxic lymphocytes. Increased severity of the disease is consistent with activation of B cell compartment and weaker phagocytic function of neutrophils.Significant differences were revealed in spontaneous and induced production of IFNγ, IL-2 and IL-8 between various groups of patients with FCT. The alterations of immune and cytokine status in a certain clinical subgroup with progressing FCT were indicative for depletion of immune system potential. As based on these data, we have established some criteria in order to assess severity of immune pathology in the patients with progressing FCT which may be of predictive value for evaluating trends in development of the specific process and feasibility of immune correction therapy