Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus.
Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae. Patients with diabetes demonstrated a lower frequency of total CD+T-cells, which showed a significant inverse association with elevated fasting blood glucose. Measurement of specific subsets indicated that those with diabetes had, low intracellular levels of interleukin (IL)-17, and lower pathogen-specific memory CD4+ and IL-17+ cell numbers. No significant difference was observed in the frequency of CD4+ and Th17 cells between those with and without diabetes. However, stratification of data by obesity indicated a significant increase in frequency of CD4+ and Th17 cells in obese individuals with diabetes compared with nonobese individual with diabetes. The memory CD+T-cell response was associated inversely with both fasting blood glucose and percent glycated hemoglobin A1c. This study demonstrated that those with type 2 diabetes have a diminished pathogen-specific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation.
Division of Epidemiology, Human Genetics and Environmental Health Sciences, School of Public Health, University of Texas Health Science Center, Brownsville Regional Campus, Brownsville, Tex.
Perla J
PJ
Martinez
Division of Epidemiology, Human Genetics and Environmental Health Sciences, School of Public Health, University of Texas Health Science Center, Brownsville Regional Campus, Brownsville, Tex.
Christine
C
Mathews
Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center, Houston, Tex.
Jeffrey K
JK
Actor
Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center, Houston, Tex.
Shen-An
SA
Hwang
Division of Epidemiology, Human Genetics and Environmental Health Sciences, School of Public Health, University of Texas Health Science Center Houston, Houston, Tex.
Eric L
EL
Brown
University of Texas Health Science Center, San-Antonio-Edinburg Regional Academic Health Center, San Antonio, Tex.
Heather K
HK
De Santiago
Division of Epidemiology, Human Genetics and Environmental Health Sciences, School of Public Health, University of Texas Health Science Center, Brownsville Regional Campus, Brownsville, Tex.
Susan P
SP
Fisher Hoch
Division of Epidemiology, Human Genetics and Environmental Health Sciences, School of Public Health, University of Texas Health Science Center, Brownsville Regional Campus, Brownsville, Tex.
Joseph B
JB
McCormick
Division of Epidemiology, Human Genetics and Environmental Health Sciences, School of Public Health, University of Texas Health Science Center, Brownsville Regional Campus, Brownsville, Tex. Electronic address: Shaper.Mirza@uth.tmc.edu.
Shaper
S
Mirza
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D013296:Streptococcus pneumoniae / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007371:Interferon-gamma; D020381:Interleukin-17; C517652:hemoglobin A1c protein, human
%A1c; BMI; CCHC; CM; Cameron County Hispanic Cohort; FBG; FBS; IFN-γ; IL; MFBG; PBMC; RAGE; RPMI; Roswell Park Memorial Institute medium; T helper; T regulatory; T-helper 17; Th; Th17; Treg; body mass index; c-RPMI; central memory; fasting blood glucose; fetal bovine serum; fetal calf serum; interferon γ; interleukin; mean fasting blood glucose; percent glycated hemoglobin A1c; peripheral blood mononuclear cell; receptors for advanced glycation end products