INCREASED ACTIVATION AND EXPANSION OF A CD57+ SUBSET WITHIN PERIPHERAL CD8+ T LYMPHOCYTES IN MYCOBACTERIUM TUBERCULOSIS-INFECTED PATIENTS

Background: Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M.tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M.tuberculosis replication. Methods: In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated γδ and αβ receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant patients) and 20 control subjects, using flowcytometry. Results: We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects (P < 0.003). Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings (P < 0.002). This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ (P < 0.003). No significant changes were observed in the percentages of CD8+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects (P < 0.002), but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases (P < 0.0001). No significant changes were observed in percentages of γδ receptor-bearing T cells between different groups. Conclusion: We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype.