Immune responses in newly developed short-lived SAM mice. III. Genetic control of defective helper T-cell activity in in vitro primary antibody response.
Immune activities of newly developed, short-lived SAM-P/1 mice declined sharply after a few months of age. As early as 2 months of age, the activity of T-helper (Th) cells ('Th2'-like) in the in vitro primary antibody response was profoundly impaired, in contrast to normal activity of Th cells ('Th1'-like) engaged in cell-mediated immune responses. Thus, young SAM-P/1 mice show a functional heterogeneity of Th cells. To determine how such a 'Th2' abnormality is inherited in SAM-P/1 mice, immune activities of their hybrids and backcrosses between MHC-identical, high responder B10.BR mice were statistically assessed. The distribution of responses did not support the Mendelian single-gene determination for low responsiveness. Moreover, involvement of a single gene which exhibits incomplete dominance was ruled out because of a continuous distribution pattern of antibody response in the F2 generation. Such an analysis strongly suggests that the impaired 'Th2'-like activity of SAM-P/1 mice is under control of two genes, based on the proportion of low responders in F2 hybrids (29 out of 267, 10.8%) and on calculation according to Wright's formula (n = 1.72). Further linkage analyses suggest that one of the genes is closely linked to albino coat-colour (c) locus on chromosome 7. The putative two genes are likely to control 'differentiation' or 'maturation' of Th2-like cells defectively, but the defect is not refractory, because in vivo-primed Th cells function in vitro as do those in ordinary strains of mice. Possible mechanisms and biological significance in relation to loss of immune activity with ageing are discussed.
Hanada
K
K
Department of Senescence Biology, Faculty of Medicine, Kyoto University, Japan.
Hosono
M
M
Hosokawa
T
T
Chen
W E
WE
Tsuboyama
T
T
Takeda
T
T
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D002478:Cells, Cultured; D006824:Hybridization, Genetic; D051379:Mice; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*