The influence of costimulation and regulatory CD4+ T cells on intestinal IgA immune responses.
It is thought that IgA B-cell differentiation is highly dependent on activated CD4+ T cells. In particular, cell-cell interactions in the Peyer's patches involving CD40 and/or CD80/CD86 have been implicated in germinal-center formation and IgA B-cell development. Also soluble factors, such as IL-4, IL-5, IL-6, and TGF beta may be critical for IgA B-cell differentiation in vivo. Here we report on some paradoxical findings with regard to IgA B-cell differentiation and specific mucosal immune responses that we have recently made using gene knockout mice. More specifically, we have investigated to what extent absence of CD4+ T cells, relevant cytokines, or T-cell-B-cell interactions would influence IgA B-cell differentiation in vivo. Using CD4- or IL-4-gene knockout mice or mice made transgenic for CTLA4Ig, we found that, although specific responses were impaired, total IgA production and IgA B-cell differentiation appeared to proceed normally. However, a poor correlation was found between, on the one hand, GC formation and IgA differentiation and, on the other hand, the ability to respond to T-cell-dependent soluble protein antigens in these mice. Thus, despite the various deficiencies in CD4+ T-cell functions seemingly intact IgA B-cell development was observed.
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
E
E
Gärdby
D
D
Kagrdic
M
M
Kjerrulf
A
A
Bromander
M
M
Vajdy
E
E
Hörnquist
N
N
Lycke
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D018858:Germinal Center / Q000502:physiology; D018796:Immunoconjugates; D007070:Immunoglobulin A / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007070:Immunoglobulin A; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4; D000069594:Abatacept