Age-Sensitive T Cell Phenotypes Covary in Genetically Heterogeneous Mice and Predict Early Death From Lymphoma

Abstract

We have assessed several age-sensitive indicators of immune status in young (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see if these varied in parallel and to determine if one or more of the status indices predicted life span or cancer incidence. We report that the number of memory (i.e., CD44hi) T cells within the CD8 subset is correlated with number of memory cells in the CD4 population, and inversely correlated with the number of naive (i.e., CD45RBhi) CD4 cells at both 6 and 11 months of age, suggesting that the conversion of naive to memory cells may occur at similar rates in both T cell subsets. Mice that ranked high in the proportion of memory T cells (within the CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11 months, suggesting that the pace or extent of memory cell formation may be a consistent trait that distinguishes mice at least within a genetically heterogeneous population. Mice that at 6 months of age exhibited high levels of CD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T cells able to proliferate in response to Con A and IL-2 were found to be significantly more likely than their littermates to die within the first 18 months of life. Cases of follicular cell lymphoma, lymphocytic and lymphoblastic lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at early ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of Immunological Markers in Predicting Responsiveness to Influenza Vaccination in Elderly Individuals

“…Therefore, an expansion of this subset at the expense of the naive population would compromise the ability to generate an immune response to new antigens, which is required to recognize the antigenic drifts of the influenza virus hemagglutinins. Indeed, animal data support the notion that CD45 isoforms may be useful markers of immunosenescence (30). Our studies have clearly shown that this is not the case.…”

Age-Dependent Alterations in the Assembly of Signal Transduction Complexes at the Site of T Cell/APC Interaction

“…The strong correlations, among individual cells, between LAT and PKC-redistribution, and between LAT migration and NF-ATc translocation, together with the ability of LAT, Vav, and PKCresponses to discriminate between agonist and nonagonist peptides in the TCR transgenic models, suggest strongly that the age-related decline in translocation of these plasma membrane proteins to the synapse may account for much of the decline with age in NF-ATc translocation and subsequent downstream changes in IL-2 gene expression. We have also found that a subset of CD4 memory T cells characterized by poor proliferation, low cytokine production, poor calcium signal generation, and high expression of P-glycoprotein (45,46) also exhibits diminished relocalization of LAT and PKC-, and diminished nuclear translocation of NF-ATc, in response to 2C11 conjugation, 4 lending further support to the idea that altered migration of proteins to the synapse is associated with, and probably contributes to, deficits in downstream signals and functional responsiveness. TCR-mediated stimulation leads to formation of an F-actin cap at the T cell-APC contact zone, and organization of supramolecular activation clusters (SMACs) (10).…”

Cachexia in the non‐obese diabetic mouse is associated with CD4+ T‐cell lymphopenia

“…A deficiency in CD4 + T cells that express a low density of the cell surface marker CD44 (CD44 low ) is associated with aging, 27,28 and with the development of spontaneous tumours. 29 CD44 is one of the cell surface markers used to distinguish antigen-inexperienced (naïve) from antigen-experienced (memory) CD4 + T cells in the mouse. Naïve CD4 + T cells express CD44 low and a high density of CD62 ligand (CD62L high ), while memory cells express CD44 at a high density (CD44 high ).…”