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Prospective monitoring reveals dynamic levels of T cell immunity to Mycobacterium tuberculosis in HIV infected individuals.

Mitchell JE, Chetty S, Govender P, Pillay M, Jaggernath M, Kasmar A, Ndung'u T, Klenerman P, Walker BD, Kasprowicz VO - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Ragon Institute of MGH, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
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.

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Related in: MedlinePlus

In- vitro culture reveals RD1-specific T cell responses.Left-hand panel displays ex vivo IFN-gamma Elispot data from 4 individuals (SK378, SK383, SK167, and SK325) who were ex vivo Elispot negative at 2 time-points 3 months apart. Right-hand panel displays data from the same individuals following a cultured Elispot (14 day in vitro culture of PBMC with the ESAT-6 or CFP-10 peptides followed by IFN-gamma Elispot). All individuals had CD4 counts above 250.
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pone-0037920-g004: In- vitro culture reveals RD1-specific T cell responses.Left-hand panel displays ex vivo IFN-gamma Elispot data from 4 individuals (SK378, SK383, SK167, and SK325) who were ex vivo Elispot negative at 2 time-points 3 months apart. Right-hand panel displays data from the same individuals following a cultured Elispot (14 day in vitro culture of PBMC with the ESAT-6 or CFP-10 peptides followed by IFN-gamma Elispot). All individuals had CD4 counts above 250.

Mentions: Our results above indicate that many MTB-specific T cell populations may lie close to (but either side of) the ex vivo RD1-Elispot cut-off. To address whether sub-threshold responses existed we performed Cultured RD1-Elispots to assess the proportion of individuals with MTB specific memory responses which were not detected in the ex vivo RD1-Elispot assay [32], [33]. 13 (62%) out of 21 individuals (who were negative by ex vivo RD1- Elispot) were positive by cultured Elispot (responses ranging from 30–475 SFC/million PBMC) (data not shown and figure 4). These data indicate that MTB-specific responses may exist in a large fraction of individuals who are RD1-Elispot negative.


Prospective monitoring reveals dynamic levels of T cell immunity to Mycobacterium tuberculosis in HIV infected individuals.

Mitchell JE, Chetty S, Govender P, Pillay M, Jaggernath M, Kasmar A, Ndung'u T, Klenerman P, Walker BD, Kasprowicz VO - PLoS ONE (2012)

In- vitro culture reveals RD1-specific T cell responses.Left-hand panel displays ex vivo IFN-gamma Elispot data from 4 individuals (SK378, SK383, SK167, and SK325) who were ex vivo Elispot negative at 2 time-points 3 months apart. Right-hand panel displays data from the same individuals following a cultured Elispot (14 day in vitro culture of PBMC with the ESAT-6 or CFP-10 peptides followed by IFN-gamma Elispot). All individuals had CD4 counts above 250.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369919&req=5

pone-0037920-g004: In- vitro culture reveals RD1-specific T cell responses.Left-hand panel displays ex vivo IFN-gamma Elispot data from 4 individuals (SK378, SK383, SK167, and SK325) who were ex vivo Elispot negative at 2 time-points 3 months apart. Right-hand panel displays data from the same individuals following a cultured Elispot (14 day in vitro culture of PBMC with the ESAT-6 or CFP-10 peptides followed by IFN-gamma Elispot). All individuals had CD4 counts above 250.
Mentions: Our results above indicate that many MTB-specific T cell populations may lie close to (but either side of) the ex vivo RD1-Elispot cut-off. To address whether sub-threshold responses existed we performed Cultured RD1-Elispots to assess the proportion of individuals with MTB specific memory responses which were not detected in the ex vivo RD1-Elispot assay [32], [33]. 13 (62%) out of 21 individuals (who were negative by ex vivo RD1- Elispot) were positive by cultured Elispot (responses ranging from 30–475 SFC/million PBMC) (data not shown and figure 4). These data indicate that MTB-specific responses may exist in a large fraction of individuals who are RD1-Elispot negative.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Ragon Institute of MGH, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus