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 gamma-delta and alpha-beta 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 gamma-delta receptor-bearing T cells between different groups.


CONCLUSIONS
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.
Fateminasab
Farah-Dokht
FD
Department of Immunology, Iran University of Medical Sciences, Tehran, Iran.
Shahgasempour
Shapour
S
Mirsaeidi
Seyed-Mehdi
SM
Tabarsi
Payam
P
Mansoori
Seyed-Davood
SD
Entezami
Zinat
Z
D000954:Antigens, Surface; D018106:CD28 Antigens / Q000032:analysis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018959:CD57 Antigens / Q000032:analysis* / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D018920:Coculture Techniques; D005434:Flow Cytometry; D006684:HLA-DR Antigens; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010641:Phenotype; D012044:Regression Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology
D000954:Antigens, Surface; D018106:CD28 Antigens; D018959:CD57 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens