Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses

SM Eaton, EM Burns, K Kusser, TD Randall… - The Journal of …, 2004 - rupress.org
SM Eaton, EM Burns, K Kusser, TD Randall, L Haynes
The Journal of experimental medicine, 2004rupress.org
With increasing age, the ability to produce protective antibodies in response to immunization
declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of
age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model
that allows us to compare identical numbers of antigen-specific naive T cells from young and
aged TCR transgenic (Tg) donors. Upon transfer of aged donor CD4 T cells to young hosts,
there was significantly reduced expansion and germinal center (GC) differentiation of the …
With increasing age, the ability to produce protective antibodies in response to immunization declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model that allows us to compare identical numbers of antigen-specific naive T cells from young and aged TCR transgenic (Tg) donors. Upon transfer of aged donor CD4 T cells to young hosts, there was significantly reduced expansion and germinal center (GC) differentiation of the antigen-specific B cell population after immunization. This reduced cognate helper function was seen at all time points and over a wide range of donor cell numbers. In hosts receiving aged CD4 cells, there were also dramatically lower levels of antigen-specific IgG. These age-related defects were not due to defects in migration of the aged CD4 T cells, but may be attributable to reduced CD154 (CD40L) expression. Furthermore, we found that there was no difference in B cell expansion and differentiation or in IgG production when young CD4 T cells were transferred to young or aged hosts. Our results show that, in this model, age-related reductions in the cognate helper function of CD4 T cells contribute significantly to defects in humoral responses observed in aged individuals.
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