Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses.
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.
Eaton
Sheri M
SM
Trudeau Institute, 154 Algonquin Ave., Saranac Lake, NY 12983, USA.
Burns
Eve M
EM
Kusser
Kimberly
K
Randall
Troy D
TD
Haynes
Laura
L
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates / Q000008:administration & dosage / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D007074:Immunoglobulin G; D009596:Nitrophenols; D010648:Phenylacetates; D011948:Receptors, Antigen, T-Cell; C026242:4-hydroxy-5-nitrophenyl acetic acid