Prospective monitoring reveals dynamic levels of T cell immunity to Mycobacterium tuberculosis in HIV infected individuals.
Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3-21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from -150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r=0.6527, p=0.0114; IP-10: r=0.6967, p=0.0056; IP-10+MIG: r=0.7055, p=0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting.
Ragon Institute of MGH, Harvard Medical School, Boston, Massachusetts, United States of America.
Jessica E
JE
Mitchell
Shivan
S
Chetty
Pamla
P
Govender
Mona
M
Pillay
Manjeetha
M
Jaggernath
Anne
A
Kasmar
Thumbi
T
Ndung'u
Paul
P
Klenerman
Bruce D
BD
Walker
Victoria O
VO
Kasprowicz
D018791:CD4 Lymphocyte Count; D054357:Chemokine CXCL10 / Q000235:genetics; D054370:Chemokine CXCL9 / Q000235:genetics; D060085:Coinfection / Q000175:diagnosis / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D057230:Limit of Detection; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology*; D019562:Viral Load
C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9