Differential responses of CD4+CD45RA+ and CD4+CD29+ subsets to activated CD8+ cells: enhanced stimulation of the CD4+CD45RA+ subset by cells from patients with multiple sclerosis.
To examine whether functionally different CD4+ cells respond uniformly to the immunoregulatory influences of allogeneic activated CD8+ cells (*CD8+), we subfractionated the CD4+ population into two subsets, based on the high expression of either CD45RA or CD29. We confirmed that the CD45RA+ cells proliferated poorly in response to soluble anti-CD3 mAb, compared to the vigorous response obtained with the CD29+ subset; the CD45RA+ cells were more responsive to stimulation with Con A. Using normal healthy controls, we found that whereas *CD8+ had a significant suppressive effect on the proliferation of the CD29+ subset, they augmented the mitogen-induced proliferative response of the CD45RA+ cells. We further demonstrated that *CD8+ derived from MS patients augmented the response of the CD45RA+ subset to a significantly higher degree compared to healthy age- and sex-matched controls. There were no significant differences between the degree of suppression exerted by the *CD8+ of either the MS or the control group on the CD29+ cells. These results demonstrate that helper/memory CD4+CD29+ cells are more sensitive to the suppressive influences of *CD8+ compared to the CD4+CD45RA+ subset. In addition, in MS, *CD8+ may contribute to a more pronounced "on" signal for virgin CD4+CD45RA+ cells, which might serve as a means to perpetuate the autoimmune disease process.
Freedman
M S
MS
Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Québec, Canada.
Blain
M
M
Antel
J P
JP
D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens; D005260:Female; D006649:Histocompatibility Antigens / Q000032:analysis*; D006801:Humans; D019012:Integrin beta1; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D019012:Integrin beta1; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens