Induction of CD4 T cell proliferation and in vitro Th1-like cytokine responses to measles virus.
Mechanisms that lead to induction of life-long immunity to measles virus (MV) are poorly understood. In the present study, we have assessed the activation, proliferation and cytokine secreting function of peripheral blood T cells from MV immune individuals. Expression of cell blastogenesis markers, such as increased forward light scatter and CD38 expression, peaked 5-7 days after infection of peripheral blood mononuclear cells (PBMC) with the live attenuated Edmonston strain of MV. Subset analysis revealed that both CD3- and CD3+ cells expressed activation markers but that the CD3+ T cells predominated late in the culture period corresponding to maximal proliferation and cell recovery. The majority of CD3+ T cells consisted of CD4+CD8- cells. IFN-gamma and IL-4 production similarly showed optimal production late in culture. Depletion of CD4 cells prior to culture and MV stimulation completely abrogated both IFN-gamma and IL-4 production, whereas depletion of CD8 cells did not diminish production, suggesting that CD4+CD8- T cells were principally involved in production of these cytokines. Finally, optimal IFN-gamma production was elicited at high MV doses and IL-4 at much lower doses. These results suggest that among MV immune individuals, in vitro responses to measles are dominated by CD4+ T cells that, depending on antigen dose, primarily produce a Th1-like and, to a lesser extent, a Th1/Th2-mixed pattern of cytokine release.
Howe
R C
RC
Mayo Vaccine Research Group, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA.
Dhiman
N
N
Ovsyannikova
I G
IG
Poland
G A
GA
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008457:Measles / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D016895:Culture Media, Serum-Free; D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma