title: Filarial infection modulates the immune response to Mycobacterium tuberculosis through expansion of CD4+ IL-4 memory T cells.
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.
authors: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and chatterjees3@mail.nih.gov.
authors: Soumya
authors: S
authors: Chatterjee
authors: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Carolyn E
authors: CE
authors: Clark
authors: Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors: Enrico
authors: E
authors: Lugli
authors: Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors: Mario
authors: M
authors: Roederer
authors: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Thomas B
authors: TB
authors: Nutman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D055985:Latent Tuberculosis / Q000276:immunology* / Q000382:microbiology; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008117:Loa / Q000276:immunology* / Q000502:physiology; D008118:Loiasis / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D001426:Bacterial Proteins; C515370:CCR7 protein, human; C117940:CFP-10 protein, Mycobacterium tuberculosis; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D017493:Leukocyte Common Antigens