Antigen-specific CD8+ T cells inhibit IgE responses and interleukin-4 production by CD4+ T cells.
There is a growing body of evidence which suggests that CD8+ T cells play an important part in regulating the IgE response to non-replicating antigens. In this study we have systematically investigated their role in the regulation of IgE and of CD4+ T cell responses to ovalbumin (OVA) by CD8+ T cell depletion in vivo. Following intraperitoneal immunization with alum-precipitated OVA, OVA-specific T cell responses were detected in the spleen and depletion of CD8+ T cells in vitro significantly enhanced the proliferative response to OVA. Depletion of CD8+ T cells in vivo 7 days after immunization failed to enhance IgE production, while depletion of CD8+ T cells on days 12-18 greatly enhanced the IgE response, which rose to 26 micrograms/ml following a second injection of anti-CD8 on day 35 and remained in excess of 1 microgram/ml over 300 days afterwards. Reconstitution on day 21 of rats CD8-depleted on day 12 with purified CD8+ T cells from animals immunized on day 12 completely inhibited the IgE response. This effect was antigen specific; CD8+ T cells from OVA-primed animals had little effect on the IgE response of bovine serum albumin immunized rats. In vivo, CD8+ T cell depletion decreased interferon (IFN)-gamma production but enhanced interleukin (IL)-4 production by OVA-stimulated splenic CD4+ T cells. Furthermore, CD8+ T cell depletion and addition of anti-IFN-gamma antibody enhanced IgE production in vitro in an IL-4-supplemented mixed lymphocyte reaction. These data clearly show that antigen-specific CD8+ T cells inhibit IgE in the immune response to non-replicating antigens. The data indicate two possible mechanisms: first, CD8+ T cells have direct inhibitory effects on switching to IgE in B cells and second, they inhibit OVA-specific IL-4 production but enhance IFN-gamma production by CD4+ T cells.
Holmes
B J
BJ
Department of Immunology, King's College School of Medicine and Dentistry, London, GB.
MacAry
P A
PA
Noble
A
A
Kemeny
D M
DM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008212:Lymphocyte Depletion; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D013154:Spleen / Q000276:immunology
D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin