TY - JOUR
T1 - Filarial infection modulates the immune response to mycobacterium tuberculosis through expansion of CD4+ IL-4 memory T cells
AU - Chatterjee, Soumya
AU - Clark, Carolyn E.
AU - Lugli, Enrico
AU - Roederer, Mario
AU - Nutman, Thomas B.
PY - 2015/3/15
Y1 - 2015/3/15
N2 - Exaggerated CD4+ T helper 2-specific cytokine producing memory T cell responses developing concomitantly with a T helper 1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis. To assess the dynamics of Ag-specific memory T cell compartments in the context of filarial infection, we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial-infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial Ag (BmA) or with the M. tuberculosis-specific Ag culture filtrate protein-10 (CFP-10). Our data demonstrated that the Inf group had a marked increase in BmA-specific CD4+IL-4+ cells (median net frequency compared with baseline [Fo] = 0.09% versus 0.01%; p = 0.038) but also to CFP-10 (Fo = 0.16% versus 0.007%; p = 0.04) and staphylococcal enterotoxin B (Fo = 0.49% versus 0.26%; p = 0.04). The Inf subjects showed a BmA-specific expansion of CD4+CD45RO+IL-4+ producing central memory (TCM, CD45RO+ CCR7+CD27+; Fo = 1.1% versus 0.5%; p = 0.04) as well as effector memory (TEM, CD45RO+CCR72CD272; Fo = 1.5% versus 0.2%; p = 0.03) with a similar but nonsignificant response to CFP-10. In addition, there was expansion of CD4+IL-4+CD45RA+ CCR7+CD27+ (naive-like) in Inf individuals compared with Uninf subjects. Among Inf subjects with definitive latent tuberculosis, there were no differences in frequencies of IL-4-producing cells within any of the memory compartments compared with the Uninf group. Our data suggest that filarial infection induces Ag-specific, exaggerated IL-4 responses in distinct T cell memory compartments to M. tuberculosis-specific Ags, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to M. tuberculosis.
AB - Exaggerated CD4+ T helper 2-specific cytokine producing memory T cell responses developing concomitantly with a T helper 1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis. To assess the dynamics of Ag-specific memory T cell compartments in the context of filarial infection, we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial-infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial Ag (BmA) or with the M. tuberculosis-specific Ag culture filtrate protein-10 (CFP-10). Our data demonstrated that the Inf group had a marked increase in BmA-specific CD4+IL-4+ cells (median net frequency compared with baseline [Fo] = 0.09% versus 0.01%; p = 0.038) but also to CFP-10 (Fo = 0.16% versus 0.007%; p = 0.04) and staphylococcal enterotoxin B (Fo = 0.49% versus 0.26%; p = 0.04). The Inf subjects showed a BmA-specific expansion of CD4+CD45RO+IL-4+ producing central memory (TCM, CD45RO+ CCR7+CD27+; Fo = 1.1% versus 0.5%; p = 0.04) as well as effector memory (TEM, CD45RO+CCR72CD272; Fo = 1.5% versus 0.2%; p = 0.03) with a similar but nonsignificant response to CFP-10. In addition, there was expansion of CD4+IL-4+CD45RA+ CCR7+CD27+ (naive-like) in Inf individuals compared with Uninf subjects. Among Inf subjects with definitive latent tuberculosis, there were no differences in frequencies of IL-4-producing cells within any of the memory compartments compared with the Uninf group. Our data suggest that filarial infection induces Ag-specific, exaggerated IL-4 responses in distinct T cell memory compartments to M. tuberculosis-specific Ags, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to M. tuberculosis.
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U2 - 10.4049/jimmunol.1402718
DO - 10.4049/jimmunol.1402718
M3 - Article
C2 - 25667413
AN - SCOPUS:84924602008
VL - 194
SP - 2706
EP - 2714
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -