The Influence of Costimulation and Regulatory CD4 super(+) T Cells on Intestinal IgA Immune Responses

• Published in: Developmental immunology Vol. 6; no. 1-2; pp. 53 - 60
• Main Authors: Gaerdby, E, Kagrdic, D, Kjerrulf, M, Bromander, A, Vajdy, M, Hoernquist, E, Lycke, N
• Format: Journal Article
• Language: English
• Published: 01-01-1998
• ISSN: 1044-6672

It is thought that IgA B-cell differentiation is highly dependent on activated CD4 super(+) 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 super(+) 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 super(+) T-cell functions seemingly intact IgA B-cell development was observed.