Mice transgenic for a soluble form of murine cytotoxic T lymphocyte antigen 4 are refractory to murine acquired immune deficiency sydrome development.
Interactions between B and CD4+ T cells are central to the pathogenesis of retrovirus-induced murine acquired immune deficiency virus (MAIDS). Prompted by previous work showing that treatment with cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4Ig) partly inhibited the disease, we studied the course of infection in mice deficient for CD28-B7 interactions (mCTLA4-Hgamma1 transgenic mice). Despite a relative viral load identical to that of non-transgenic mice, the transgenic mice did not develop any of the major MAIDS symptoms (i.e. lymphoproliferation and immune anergy). The mCTLA4-Hgamma1 did not however, completely inhibit B-cell activation as indicated by a slight hypergammaglobulinaemia and microscopic blastic transformation. Absence of MAIDS in transgenic mice was associated with much lower levels of both interleukin-4 and interferon-gamma transcripts following viral infection. These results support the theory that the CD28/B7 costimulatory pathway is a critical determinant to MAIDS development.
De Leval
L
L
Laboratory of Pathology, University of Liège, Liège, Belgium.
Debrus
S
S
Lane
P
P
Boniver
J
J
Moutschen
M
M
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D002455:Cell Division; D016207:Cytokines / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016906:Interleukin-9 / Q000235:genetics; D008214:Lymphocytes; D051379:Mice; D008822:Mice, Transgenic; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D007074:Immunoglobulin G; D018793:Interleukin-13; D019409:Interleukin-15; D015848:Interleukin-5; D015850:Interleukin-6; D016906:Interleukin-9; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D000069594:Abatacept; D007371:Interferon-gamma