Filarial infection modulates the immune response to Mycobacterium tuberculosis through expansion of CD4+ IL-4 memory T cells

J Immunol. 2015 Mar 15;194(6):2706-14. doi: 10.4049/jimmunol.1402718. Epub 2015 Feb 9.

Abstract

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(+)CCR7(-)CD27(-); 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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, Helminth / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Memory / immunology*
  • Interleukin-4 / immunology*
  • Interleukin-4 / metabolism
  • Latent Tuberculosis / immunology*
  • Latent Tuberculosis / microbiology
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Loa / immunology*
  • Loa / physiology
  • Loiasis / immunology*
  • Loiasis / parasitology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / physiology
  • Receptors, CCR7 / immunology
  • Receptors, CCR7 / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Young Adult

Substances

  • Antigens, Bacterial
  • Antigens, Helminth
  • Bacterial Proteins
  • CCR7 protein, human
  • CFP-10 protein, Mycobacterium tuberculosis
  • Receptors, CCR7
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interleukin-4
  • Leukocyte Common Antigens