The influence of costimulation and regulatory CD4+ T cells on intestinal IgA immune responses

• Published in: Clinical & developmental immunology Vol. 6; no. 1-2; pp. 53 - 60
• Main Authors: Gärdby, E, Kagrdic, D, Kjerrulf, M, Bromander, A, Vajdy, M, Hörnquist, E, Lycke, N
• Format: Journal Article
• Language: English
• Published: England Hindawi Publishing Corporation 1998; Hindawi Limited
• Subjects: Abatacept; Animals; Antigens; Antigens, CD; Antigens, Differentiation - physiology; B-Lymphocytes; B-Lymphocytes - physiology; Basic Medicine; Biological Sciences; Biologiska vetenskaper; biosynthesis; CD4-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes - physiology; CD40 Ligand; Cell Differentiation; CTLA-4 Antigen; Differentiation; genetics; Germinal Center; Germinal Center - physiology; Immunoconjugates; Immunoglobulin A; Immunoglobulin A - biosynthesis; immunology; Interleukin-4; Interleukin-4 - genetics; Interleukin-4 - physiology; Interleukin-6; Interleukin-6 - genetics; Interleukin-6 - physiology; Intestinal Mucosa; Intestinal Mucosa - immunology; Knockout; Medicinska grundvetenskaper; Membrane Glycoproteins; Membrane Glycoproteins - physiology; Mice; Mice, Knockout; physiology
• ISSN: 1044-6672; 2314-8861; 1740-2522; 2314-7156; 1740-2530
• DOI: 10.1155/1998/75718

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.