The CD8 T cell compartment plays a dominant role in the deficiency of Brown-Norway rats to mount a proper type 1 immune response.
Differential cytokine production by T cells plays an important role in regulating the nature of an immune response. In the rat, Brown-Norway (BN) and Lewis (LEW) strains differ markedly in their susceptibility to develop either type 1 or type 2-mediated autoimmune manifestations. BN rats are susceptible to type 2-dependent systemic autoimmunity, while LEW rats are resistant. Conversely, type 1-mediated, organ-specific autoimmune disease can be easily induced in LEW, but not in BN, rats. The mechanisms involved in the differential development of type 1 and type 2 immune responses by these two strains are still unknown. In the present study we analyzed the contributions of APC, CD4 and CD8 T cells, and MHC molecules in the difference between LEW and BN rats to develop a type 1 immune response. First, we show that the defect of BN T cells to produce type 1 cytokines in vitro does not require the presence of APC and, by using an APC-independent stimulation assay, we have localized the defect within the T cell compartment. Both CD4 and CD8 T cells are involved in the defect of BN rats to develop a type 1 immune response with a major contribution of the CD8 T cell compartment. This defect is associated with an increase in the type 2 cytokine IL-4 in both BN T cell populations, but neutralization of this cytokine does not restore this defect. Finally, by using MHC congenic rats, we show that the MHC haplotype is not involved in the defect of BN T cells to mount a proper type 1 cytokine response.
Cautain
Bastien
B
Institut National de la Santé et de la Recherche Médicale, Unité 28, Institut Fédératif de Recherche 30, Hôpital Purpan and Université Paul Sabatier, place du Dr. Baylac, 31059 Toulouse, France.
Damoiseaux
Jan
J
Bernard
Isabelle
I
Xystrakis
Emmanuel
E
Fournié
Emmanuelle
E
van Breda Vriesman
Peter
P
Druet
Philippe
P
Saoudi
Abdelhadi
A
D000818:Animals; D020296:Animals, Congenic; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006649:Histocompatibility Antigens / Q000502:physiology; D007136:Immunoglobulins / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D006649:Histocompatibility Antigens; D007136:Immunoglobulins; D018664:Interleukin-12; D015847:Interleukin-4