Helminth antigens selectively differentiate unsensitized CD45RA+ CD4+ human T cells in vitro.
Human filarial helminth infections are characterized by type 2 immune responses to parasite Ag that can persist for the life of the individual; one possible cause for this may be prenatal exposure to the blood-borne microfilarial (Mf) stage of the parasite. To examine the relationship between early exposure to filarial Ag and subsequent immune responsiveness, CD45RA+ CD4+ cells frp, normal unsensitized donors were stimulated in vitro with soluble microfilarial Ag (MfAg) from the filarial parasite Brugia malayi in the presence of APCs. MfAg alone induced proliferation and IFN-gamma and IL-5 production in unsensitized CD45RA+ CD4+ cells, demonstrating the ability of filarial Ags to prime naive T cells in the absence of exogenous cytokines and dendritic cells. Adding exogenous cytokine(s) (particularly IL-12 and IL-4) during priming was able to alter the MfAg-specific responses of CD45RA+ CD4+ cells as well as subsequent responses to Ag. Interestingly, priming solely with MfAg led to enhanced IL-5 production following Ag restimulation, suggesting that MfAg preferentially primes for type 2 responses. These data demonstrate that filarial Ags by themselves can specifically prime CD45RA+ CD4+ cells in vitro and do so in such a way as to deviate the immune response.
Steel
C
C
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. cathy_steel@nih.gov
Nutman
T B
TB
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005368:Filariasis / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D015848:Interleukin-5 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000947:Antigens, Helminth; D016207:Cytokines; D015848:Interleukin-5; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens