The Journal of Experimental Medicine
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Published 20 December 2004. doi:10.1084/jem.20041395
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 12, 1613-1622
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Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses

Sheri M. Eaton, Eve M. Burns, Kimberly Kusser, Troy D. Randall, and Laura Haynes

Trudeau Institute, Saranac Lake, NY 12983

Address correspondence to Laura Haynes, Ph.D., Trudeau Institute, 154 Algonquin Ave., Saranac Lake, NY 12983. Phone: (518) 891-3080 (x374); Fax: (518) 891-5126; email: lhaynes{at}trudeauinstitute.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 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.

Key Words: aging • B lymphocytes • germinal centers • antibody • vaccines


Abbreviations used in this paper: CFSE, carboxy fluorescein succinimidyl ester; FDC, follicular dendritic cell; GC, germinal center; NP, 4-hydroxy-3-nitrophenyl acetyl; NP-APC, NP conjugated to allophycocyanin; PCC, pigeon cytochrome c; PNA, peanut agglutinin; Tg, transgenic.


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